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El-Sawaf AK, Abdelgawad AM, Nassar AA, Elsherbiny DA. Immobilization of biosynthesized gallium nanoparticles in Polyvinylpyrrolidone/Sodium alginate films: Potent bactericidal protection against food spoilage bacteria. Int J Biol Macromol 2024; 274:133438. [PMID: 38936583 DOI: 10.1016/j.ijbiomac.2024.133438] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2024] [Revised: 06/17/2024] [Accepted: 06/24/2024] [Indexed: 06/29/2024]
Abstract
The increasing threat of spoilage bacterial infections, driven by the resistance of bacteria to many antimicrobial treatments, is a significant worldwide public health problem, especially concerning food preservation. To tackle these difficulties, this research investigates the possibility of using packaging sheets that include antimicrobial agents and increasing the prolonged storage time by preventing the bioburden of foodborne pathogens. This approach uses metal nanoparticles' ability to prevent harmful bacteria that cause food spoiling. Gallium nanoparticles (GaNPs) were created using a water-based extract from Andrographis paniculata leaves as a bioreducing agent. The GaNPs were added to a film made of sodium alginate (SA) and polyvinylpyrrolidone (PVP). The study showed that incorporating GaNPs into polymer films resulted in films with a desirable contact angle and decreased water vapor permeability. Significantly, the developed films demonstrated increased efficiency against E.coli O157 compared to other species. Also, it exhibited increased vulnerability to bacterial strains at the biofilm stage, surpassing PVP-SA/GaNPs-0. Remarkably, the toxicity tests showed that the films exhibited no cytotoxicity. Overall, the films indicated their potential for avoiding bacterial bioburden, prolonging the shelf life of perishable products, and contributing to diverse antimicrobial applications in the food industry.
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Affiliation(s)
- Ayman K El-Sawaf
- Department of Chemistry, College of Science and Humanities, Prince Sattam bin Abdulaziz University, Alkharj 11942, Saudi Arabia; Department of Chemistry, Faculty of Science, Menoufia University, Shibin El-Kom, Egypt
| | - Abdelrahman M Abdelgawad
- Textile Research and Technology Institute, National Research Center (Affiliation ID: 60014618), 12622, Dokki, Giza, Egypt; Textile Engineering Chemistry and Science Department, Wilson College of Textiles, North Carolina State University, Raleigh, NC, USA
| | - Amal A Nassar
- Department of Chemistry, College of Science and Humanities, Prince Sattam bin Abdulaziz University, Alkharj 11942, Saudi Arabia
| | - Dalia A Elsherbiny
- Department of Chemistry, College of Science and Humanities, Prince Sattam bin Abdulaziz University, Alkharj 11942, Saudi Arabia; Department of Chemistry, Faculty of Science, Menoufia University, Shibin El-Kom, Egypt.
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Pasha A, Kumar K, Heena SK, Arnold Emerson I, Pawar SC. Inhibition of NF-kB and COX-2 by andrographolide regulates the progression of cervical cancer by promoting PTEN expression and suppressing PI3K/AKT signalling pathway. Sci Rep 2024; 14:12020. [PMID: 38797813 PMCID: PMC11128455 DOI: 10.1038/s41598-024-57304-7] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2023] [Accepted: 03/16/2024] [Indexed: 05/29/2024] Open
Abstract
In the face of recent advances in Cervical cancer (CC) treatment, therapeutic and surgical procedures for CC management are still inadequate. In the current study for the first time Andrographolide (Andro) has been explored for its multitarget therapeutic efficacy on NF-kB, COX-2, and PI3K/AKT expressions together in CC. The expression levels of NF-kB, COX-2, PI3K and PTEN in the CC patient samples, both at mRNA and protein levels have shown significant association with poor survival and increased tumor aggressiveness. The binding efficacy of Andro was investigated using molecular docking and molecular dynamic simulations, and the protein and ligand complex for NF-kB and COX-2 has shown high binding energy. Andro displayed cytotoxicity by impeding the in-vitro proliferation of CC cells. Andro significantly supressed the NF-kB, COX-2, and PI3K expression and enhanced the expression levels of PTEN at protein levels in-vitro. Andro induced apoptosis in a dose dependent manner and significantly inhibited the migration and invasion of CC cells. Andro exhibited similar activity in-vivo and suppressed the CC tumor growth in xenograft C57BL/6 mice model. The anti-tumor activity of Andro, both in-vitro and in-vivo has shown considerable downregulation of NF-kB and COX-2 and induced apoptosis through impeding the PI3K/AKT signalling pathway. These findings from the above study projects, administration of Andro as an effective alternate safe compound to curtail and impede cervical cancer progression.
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Affiliation(s)
- Akbar Pasha
- Department of Genetics and Biotechnology, University College of Science, Osmania University, Hyderabad, Telangana, 500007, India
| | - Kiran Kumar
- Department of Bioinformatics, School of Biosciences and Technology, Vellore Institute of Technology, Vellore, Tamil Nadu, 632014, India
| | - S K Heena
- Department of Pathology, Osmania Medical College, Hyderabad, Telangana, 500095, India
| | - I Arnold Emerson
- Department of Bioinformatics, School of Biosciences and Technology, Vellore Institute of Technology, Vellore, Tamil Nadu, 632014, India
| | - Smita C Pawar
- Department of Genetics and Biotechnology, University College of Science, Osmania University, Hyderabad, Telangana, 500007, India.
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Siripongboonsitti T, Ungtrakul T, Tawinprai K, Auewarakul C, Chartisathian W, Jansala T, Julsawad R, Soonklang K, Mahanonda N, Mahidol C. Efficacy of Andrographis paniculata extract treatment in mild to moderate COVID-19 patients being treated with favipiravir: A double-blind, randomized, placebo-controlled study (APFaVi trial). PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2023; 119:155018. [PMID: 37625206 DOI: 10.1016/j.phymed.2023.155018] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/05/2022] [Revised: 07/08/2023] [Accepted: 08/08/2023] [Indexed: 08/27/2023]
Abstract
BACKGROUND While favipiravir had been the standard anti-SARS-CoV-3 drug for COVID-19 treatment in Thailand, the efficacy of favipiravir treatment is controversial. Andrographis paniculata extract (APE) inhibits viral entry, exhibits immunomodulatory effects, and proposes to have the potential for early-stage COVID-19 treatment. METHODS A randomized, double-blind, placebo-controlled trial was performed in Thailand during June - September 2021. Non-severe COVID-19 patients were randomized 1:1 to groups receiving 180 mg/day of APE plus favipiravir (APE-FPV group) or placebo plus favipiravir (placebo-FPV group). Efficacy in preventing disease progression to severe COVID-19 was assessed on day 4, using World Health Organization Clinical Progression Scale (WHOCPS) score and visual analog scale (VAS) for acute respiratory tract infection symptoms. RESULTS Of 146 patients, there were 73 patients in each group. Non-deterioration of WHOCPS scores on day 4 was 98.63% versus 97.26% of patients in the APE-FPV and placebo-FPV groups (p = 1.000). No difference in supplemental oxygen, hospitalization, and death was shown in both groups. The oxygen supplemental was 4.11% in the placebo-FPV group. The interleukin (IL)-1β was significantly lower in the APE than in the placebo-FPV group throughout the study. We found no difference in virologic outcomes between groups and no substantial adverse events. CONCLUSIONS APE treatment did not demonstrate additional clinical and virological benefits in patients with mild to moderate COVID-19 being treated with favipiravir. Early reduction of IL-1β with APE may be advantageous in preventing cytokine storms in severe COVID-19 and requires further study.
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Affiliation(s)
- Taweegrit Siripongboonsitti
- Division of Infectious Diseases, Department of Medicine, Chulabhorn Hospital, Chulabhorn Royal Academy, Bangkok, Thailand; Princess Srisavangavadhana College of Medicine, Chulabhorn Royal Academy, Bangkok, Thailand
| | - Teerapat Ungtrakul
- Princess Srisavangavadhana College of Medicine, Chulabhorn Royal Academy, Bangkok, Thailand
| | - Kriangkrai Tawinprai
- Division of Infectious Diseases, Department of Medicine, Chulabhorn Hospital, Chulabhorn Royal Academy, Bangkok, Thailand
| | - Chirayu Auewarakul
- Princess Srisavangavadhana College of Medicine, Chulabhorn Royal Academy, Bangkok, Thailand
| | - Wipada Chartisathian
- Department of Medicine, Chulabhorn Hospital, Chulabhorn Royal Academy, Bangkok, Thailand
| | - Thitikan Jansala
- Pharmacy and Medical Supplies Department, Chulabhorn Hospital, Chulabhorn Royal Academy, Bangkok, Thailand
| | - Rattana Julsawad
- Nursing Department, Chulabhorn Hospital, Chulabhorn Royal Academy, Bangkok, Thailand
| | - Kamonwan Soonklang
- Center of Learning and Research in Celebration of HRH Princess Chulabhorn's 60(th) Birthday Anniversary, Chulabhorn Royal Academy, Bangkok, Thailand
| | | | - Chulabhorn Mahidol
- Chulabhorn Royal Academy, Bangkok, Thailand; Chulabhorn Research Institute, Bangkok, Thailand
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Bhaisare S, Pathak S, Ajankar VV. Physiological Activities of the King of Bitters (Andrographis paniculata): A Review. Cureus 2023; 15:e43515. [PMID: 37719535 PMCID: PMC10501175 DOI: 10.7759/cureus.43515] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Accepted: 08/14/2023] [Indexed: 09/19/2023] Open
Abstract
Andrographis paniculata is a versatile tropical plant that is considered to have many essential medicinal properties. Plants can combine an open scope of the natural active compound that carries out significant organic roles and are used as pharmaceuticals. Herbal plants have therapeutic and prophylactic properties, so scientists are concentrating on developing crude drugs to make people's lives easier. Medicinal plants are the primary sources of therapeutic remedies for various ailments. These potential medicinal effects are primarily attributed to their active phytoconstituents. The importance of plants has been well understood by society and is well documented by scientists who have attached medicinal values to plants since ancient times. A. paniculata has been used as a herbal remedy for treating the upper gastrointestinal tract and upper respiratory tract, fever, herpes, diabetes, and other chronic illness. The A. paniculata treats a wide range of diseases in traditional medicinal systems, and its intended benefits must be evaluated. Depending on different plant studies, this review aims to discuss the medicinal values, pharmacological activity, and toxicity profile of A. paniculata like antibacterial, antioxidative, antidiabetic, anti-inflammatory, and anti-cancer activity for successful plant usage. In order to address the forthcoming research opportunities in the future, there is a need to establish a means of bridging the existing gap. It underscores the compilation of extensive pharmacological uses in order to establish the potential of A. paniculata as a versatile medicinal agent.
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Affiliation(s)
- Sweza Bhaisare
- Clinical Research, Datta Meghe Institute of Higher Education and Research, Wardha, IND
| | - Swanand Pathak
- Pharmacology, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
| | - Vaishnavi V Ajankar
- Clinical Research, Datta Meghe Institute of Higher Education and Research, Wardha, IND
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Komaikul J, Ruangdachsuwan S, Wanlayaporn D, Palabodeewat S, Punyahathaikul S, Churod T, Choonong R, Kitisripanya T. Effect of andrographolide and deep eutectic solvent extracts of Andrographis paniculata on human coronavirus organ culture 43 (HCoV-OC43). PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2023; 112:154708. [PMID: 36805485 PMCID: PMC9905047 DOI: 10.1016/j.phymed.2023.154708] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/13/2022] [Revised: 01/19/2023] [Accepted: 02/05/2023] [Indexed: 06/18/2023]
Abstract
BACKGROUND Andrographis paniculata (Burm. f.) Nees has demonstrated potential for treating infections caused by coronaviruses. However, no antiviral activity of andrographolide or A. paniculata extracts against human coronavirus organ culture 43 (HCoV-OC43) has been reported. PURPOSE This study aimed to evaluate the anti-HCoV-OC43 effect of andrographolide and A. paniculata as well as the correlation between andrographolide concentration and the anti-HCoV-OC43 activity of A. paniculata extracts. METHODS This study evaluated and compared the in vitro anti-HCoV-OC43 activities of various A. paniculata extracts and andrographolide. To obtain A. paniculata extracts with different concentrations of andrographolide and its components, methanol and deep eutectic solvents (DES) were used to extract the aerial parts of A. paniculata. Andrographolide content was determined using UV-HPLC, and antiviral activity was assessed in HCT-8 colon cells. RESULTS The methanol and five acidic DES (containing malic acid or citric acid) extracts of A. paniculata exerted anti-HCoV-OC43 activity. Antiviral activity had a moderately strong positive linear relationship (r = 0.7938) with andrographolide content. Although the methanol extract contained the highest andrographolide content (2.34 mg/ml), its anti-HCoV-OC43 activity was lower than that of the DES extracts containing lower andrographolide concentrations (0.92-1.46 mg/ml). CONCLUSION Methanol and the five acidic DES extracts of A. paniculata exhibited anti-HCoV-OC43 activity. However, the in vitro antiviral activity of A. paniculata extracts did not have a very strong positive linear relationship (r < 0.8) with andrographolide concentration in the extract. As a result, when comparing A. paniculata extracts, the anti-HCoV-OC43 test could provide a different result from the andrographolide concentration determination.
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Affiliation(s)
- Jukrapun Komaikul
- Center for Vaccine Development, Institute of Molecular Biosciences, Mahidol University, Nakhon Pathom, Thailand
| | - Sasiporn Ruangdachsuwan
- Center for Vaccine Development, Institute of Molecular Biosciences, Mahidol University, Nakhon Pathom, Thailand
| | - Duangnapa Wanlayaporn
- Center for Vaccine Development, Institute of Molecular Biosciences, Mahidol University, Nakhon Pathom, Thailand
| | - Somnuek Palabodeewat
- Center for Vaccine Development, Institute of Molecular Biosciences, Mahidol University, Nakhon Pathom, Thailand
| | - Surat Punyahathaikul
- Center for Vaccine Development, Institute of Molecular Biosciences, Mahidol University, Nakhon Pathom, Thailand
| | - Theeraporn Churod
- Center for Vaccine Development, Institute of Molecular Biosciences, Mahidol University, Nakhon Pathom, Thailand
| | | | - Tharita Kitisripanya
- Department of Pharmacognosy, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand.
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Raj JP, Maurya MR, Nair N, Marfatia H, Hadaye R, Gogtay NJ. Efficacy and safety of AP-Bio®(KalmCold®) in participants with uncomplicated upper respiratory tract viral infection (common cold) - A phase III, double-blind, parallel group, randomized placebo-controlled trial. Complement Ther Med 2023; 73:102934. [PMID: 36842634 DOI: 10.1016/j.ctim.2023.102934] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2022] [Revised: 02/16/2023] [Accepted: 02/23/2023] [Indexed: 02/26/2023] Open
Abstract
INTRODUCTION Kalmegh (Andrographis paniculata) is commonly used for treating uncomplicated Upper Respiratory Tract Infection (URTI) in complementary and alternative system of medicine. AP-Bio®(KalmCold®) is a standardized extract derived from the leaves of A. paniculata. This study was proposed to evaluate its efficacy using validated scales and objective measures. METHODS Participants were randomized in a ratio of 1:1:1 to receive either AP-Bio® 200 mg/day, AP-Bio® 400 mg/day or placebo for 7 days. The primary outcome measure was Wisconsin Upper Respiratory Symptom Survey (WURSS-21) score. The secondary outcome measures were nasal mucous weight, nasal muco-ciliary clearance function and Interleukin-8 in nasal wash, as well as safety and tolerability. RESULTS A total of n = 331 participants were screened and N = 300 participants were enrolled. The absolute WURSS-21 global score [mean (Standard Deviation - SD)] in the AP-Bio® 400 mg group [5.70 (5.31)] was less than the AP-Bio® 200 mg group [5.81 (4.83)] on Day-3. However, it was much higher in the placebo group [9.55 (14.27)]. AP-Bio® 400 mg group (Mean Difference - MD [Standard Error - SE] = -3.85 [1.52]; 95% CI = -6.85, - 0.85; adjusted p = 0.034) and 200 mg group (MD [SE] = -3.74 [1.51]; 95% CI = -6.73, - 0.76; adjusted p = 0.038) had significantly lower score than placebo. Similarly, on Day-3, the change in global score from baseline was significantly better in the AP-Bio® 400 mg group (MD [SE] = -3.91; [1.82] 95% CI = -7.50, - 0.32; adjusted p = 0.038) and AP-Bio® 200 mg group (MD [SE] = -3.84 [1.97]; 95% CI = -7.72, - 0.04; adjusted p = 0.044) in comparison to the placebo group. Nasal mucous weight, tissue paper counts used, and interleukin-8 showed a trend towards AP-Bio® groups having a favourable outcome when compared with placebo but did not reach statistical significance due to a small sample size. None of the study participants complained of any adverse physical symptoms. However, incident eosinophilia was noted in n = 20 participants on day 3. (n = 6 in AP-Bio® 200 mg group, n = 7 in Ap-Bio® 400 mg group and n = 13 in placebo group; p = 0.181). CONCLUSIONS Participants in both the AP-Bio® dose groups showed positive tendency towards resolution of URTI symptoms when compared with placebo on Day-3 but not on Day-5 and Day-7.
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Affiliation(s)
- Jeffrey Pradeep Raj
- Department of Clinical Pharmacology, Seth GS Medical College & King Edward Memorial Hospital, Mumbai 400012, Maharashtra, India.
| | - Miteshkumar Rajaram Maurya
- Department of Clinical Pharmacology, Seth GS Medical College & King Edward Memorial Hospital, Mumbai 400012, Maharashtra, India
| | - Nayana Nair
- Department of Clinical Pharmacology, Seth GS Medical College & King Edward Memorial Hospital, Mumbai 400012, Maharashtra, India
| | - Hetal Marfatia
- Department of Otorhinolaryngology, Seth GS Medical College & King Edward Memorial Hospital, Mumbai 400012, Maharashtra, India
| | - Rujuta Hadaye
- Department of Community Medicine, Seth GS Medical College & King Edward Memorial Hospital, Mumbai 400012, Maharashtra, India
| | - Nithya Jaideep Gogtay
- Department of Clinical Pharmacology, Seth GS Medical College & King Edward Memorial Hospital, Mumbai 400012, Maharashtra, India
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Okuno K, Xu C, Pascual-Sabater S, Tokunaga M, Takayama T, Han H, Fillat C, Kinugasa Y, Goel A. Andrographis Reverses Gemcitabine Resistance through Regulation of ERBB3 and Calcium Signaling Pathway in Pancreatic Ductal Adenocarcinoma. Biomedicines 2023; 11:119. [PMID: 36672630 PMCID: PMC9855441 DOI: 10.3390/biomedicines11010119] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2022] [Revised: 12/26/2022] [Accepted: 12/27/2022] [Indexed: 01/05/2023] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies, primarily due to intrinsic or acquired resistance to chemotherapy, such as Gemcitabine (Gem). Naturally occurring botanicals, including Andrographis (Andro), can help enhance the anti-tumorigenic therapeutic efficacy of conventional chemotherapy through time-tested safety and cost-effectiveness. Accordingly, we hypothesized that Andro might reverse Gem resistance in PDAC. The critical regulatory pathways associated with Gem resistance in PDAC were identified by analyzing publicly available transcriptomic profiling and PDAC tissue specimens. A series of systematic in vitro experiments were performed using Gem-resistant (Gem-R) PDAC cells and patient-derived 3D-organoids to evaluate the Andro-mediated reversal of Gem resistance in PDAC. Transcriptomic profiling identified the calcium signaling pathway as a critical regulator of Gem-resistance (Fold enrichment: 2.8, p = 0.002). Within this pathway, high ERBB3 expression was significantly associated with poor prognosis in PDAC patients. The combination of Andro and Gem exhibited superior anti-cancer potential in Gem-R PDAC cells through potentiating cellular apoptosis. The combined treatment down-regulated ERBB3 and decreased intracellular calcium concentration in Gem-R PDAC cells. Finally, these findings were successfully interrogated in patient-derived 3D-organoids. In conclusion, we demonstrate novel evidence for Andro-mediated reversal of chemoresistance to Gem in PDAC cells through the regulation of ERBB3 and calcium signaling.
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Affiliation(s)
- Keisuke Okuno
- Department of Molecular Diagnostics and Experimental Therapeutics, Beckman Research Institute of City of Hope, Biomedical Research Center, Monrovia, CA 91016, USA
- Department of Gastrointestinal Surgery, Tokyo Medical and Dental University, Tokyo 113-8510, Japan
| | - Caiming Xu
- Department of Molecular Diagnostics and Experimental Therapeutics, Beckman Research Institute of City of Hope, Biomedical Research Center, Monrovia, CA 91016, USA
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian 116004, China
| | - Silvia Pascual-Sabater
- Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain
| | - Masanori Tokunaga
- Department of Gastrointestinal Surgery, Tokyo Medical and Dental University, Tokyo 113-8510, Japan
| | - Tetsuji Takayama
- Department of Gastroenterology and Oncology, Tokushima University Graduate School, Tokushima 770-8503, Japan
| | - Haiyong Han
- Molecular Medicine Division, The Translational Genomics Research Institute, Phoenix, AZ 85004, USA
| | - Cristina Fillat
- Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain
| | - Yusuke Kinugasa
- Department of Gastrointestinal Surgery, Tokyo Medical and Dental University, Tokyo 113-8510, Japan
| | - Ajay Goel
- Department of Molecular Diagnostics and Experimental Therapeutics, Beckman Research Institute of City of Hope, Biomedical Research Center, Monrovia, CA 91016, USA
- City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA
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Yadav RP, Sadhukhan S, Saha ML, Ghosh S, Das M. Exploring the mechanism of andrographolide in the treatment of gastric cancer through network pharmacology and molecular docking. Sci Rep 2022; 12:18413. [PMID: 36319798 PMCID: PMC9626486 DOI: 10.1038/s41598-022-18319-0] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2021] [Accepted: 08/09/2022] [Indexed: 01/01/2023] Open
Abstract
Gastric cancer has emerged as a key challenge in oncology research as a malignant tumour with advanced stage detection. Apart from surgical management, a pharmacotherapeutic approach to stomach cancer treatment is an appealing option to consider. Andrographolide has been shown to have anticancer and chemosensitizer properties in a variety of solid tumors, including stomach cancer but the exact molecular mechanism is skeptical. In this study, we identified and validated pharmacological mechanism involved in the treatment of GC with integrated approach of network pharmacology and molecular docking. The targets of andrographolide and GC were obtained from databases. The intersected targets between andrographolide and GC-related genes were used to construct protein-protein interaction (PPI) network. Furthermore, mechanism of action of the targets was predicted by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Finally, these results were validated by molecular docking experiments, mRNA and protein expression level. A total of 197 targets were obtained for andrographolide treating GC. Functional enrichment analysis revealed that the target genes were exerted promising therapeutic effects on GC by HIF-1 and PI3K-Akt signaling pathway. The possible mechanism of action is by inactivation of HIF-1 signaling pathway which is dependent on the inhibition of upstream PI3K-AKT pathway. The PPI network identified SRC, AKT1, TP53, STAT3, PIK3CA, MAPK1, MAPK3, VEGFA, JUN and HSP90AA1 as potential hub targets. In addition, these results were further validated with molecular docking experiments. Survival analysis indicated that the expression levels of the hub genes were significantly associated with the clinical prognosis of GC. This study provided a novel approach to reveal the therapeutic mechanisms of andrographolide on GC, making future clinical application of andrographolide in the treatment of GC.
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Affiliation(s)
- Ravi Prakash Yadav
- grid.59056.3f0000 0001 0664 9773Department of Zoology, University of Calcutta, 35, Ballygunge Circular Road, Kolkata, 700 019 India
| | - Susanta Sadhukhan
- grid.59056.3f0000 0001 0664 9773Department of Zoology, University of Calcutta, 35, Ballygunge Circular Road, Kolkata, 700 019 India
| | - Makhan Lal Saha
- grid.414764.40000 0004 0507 4308Department of General Surgery, Institute of Post Graduate Medical Education & Research, Kolkata, 700020 India
| | - Sudakshina Ghosh
- grid.59056.3f0000 0001 0664 9773Department of Zoology, Vidyasagar College for Women, 39 Sankar Ghosh Lane, Kolkata, 700006 India
| | - Madhusudan Das
- grid.59056.3f0000 0001 0664 9773Department of Zoology, University of Calcutta, 35, Ballygunge Circular Road, Kolkata, 700 019 India
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Intharuksa A, Arunotayanun W, Yooin W, Sirisa-ard P. A Comprehensive Review of Andrographis paniculata (Burm. f.) Nees and Its Constituents as Potential Lead Compounds for COVID-19 Drug Discovery. Molecules 2022; 27:molecules27144479. [PMID: 35889352 PMCID: PMC9316804 DOI: 10.3390/molecules27144479] [Citation(s) in RCA: 31] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2022] [Revised: 07/05/2022] [Accepted: 07/11/2022] [Indexed: 11/17/2022] Open
Abstract
The COVID-19 pandemic has intensively disrupted global health, economics, and well-being. Andrographis paniculata (Burm. f.) Nees has been used as a complementary treatment for COVID-19 in several Asian countries. This review aimed to summarize the information available regarding A. paniculata and its constituents, to provide critical points relating to its pharmacological properties, safety, and efficacy, revealing its potential to serve as a source of lead compounds for COVID-19 drug discovery. A. paniculata and its active compounds possess favorable antiviral, anti-inflammatory, immunomodulatory, and antipyretic activities that could be beneficial for COVID-19 treatment. Interestingly, recent in silico and in vitro studies have revealed that the active ingredients in A. paniculata showed promising activities against 3CLpro and its virus-specific target protein, human hACE2 protein; they also inhibit infectious virion production. Moreover, existing publications regarding randomized controlled trials demonstrated that the use of A. paniculata alone or in combination was superior to the placebo in reducing the severity of upper respiratory tract infection (URTI) manifestations, especially as part of early treatment, without serious side effects. Taken together, its chemical and biological properties, especially its antiviral activities against SARS-CoV-2, clinical trials on URTI, and the safety of A. paniculata, as discussed in this review, support the argument that A. paniculata is a promising natural source for drug discovery regarding COVID-19 post-infectious treatment, rather than prophylaxis.
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Affiliation(s)
- Aekkhaluck Intharuksa
- Department of Pharmaceutical Sciences, Faculty of Pharmacy, Chiang Mai University, Chiang Mai 50200, Thailand; (A.I.); (W.Y.); (P.S.-a.)
| | - Warunya Arunotayanun
- Kanchanabhishek Institute of Medical and Public Health Technology, Praboromarajchanok Institute, Nonthaburi 11150, Thailand
- Correspondence:
| | - Wipawadee Yooin
- Department of Pharmaceutical Sciences, Faculty of Pharmacy, Chiang Mai University, Chiang Mai 50200, Thailand; (A.I.); (W.Y.); (P.S.-a.)
| | - Panee Sirisa-ard
- Department of Pharmaceutical Sciences, Faculty of Pharmacy, Chiang Mai University, Chiang Mai 50200, Thailand; (A.I.); (W.Y.); (P.S.-a.)
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Latha D, Hrishikesh D, Shiban G, Chandrashekar C, Bharath BR. In silico, in vitro screening of plant extracts for anti-SARS-CoV-2 activity and evaluation of their acute and sub-acute toxicity. PHYTOMEDICINE PLUS : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2022; 2:100233. [PMID: 35403091 PMCID: PMC8801592 DOI: 10.1016/j.phyplu.2022.100233] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/27/2021] [Revised: 01/21/2022] [Accepted: 01/29/2022] [Indexed: 04/18/2023]
Abstract
BACKGROUND In the absence of a specific drug for COVID 19, treatment with plant extracts could be an option worthy of further investigation and has motivated to evaluate the safety and anti-SARS-CoV-2 activity of plant extracts. PURPOSE To screen the phytochemicals for anti-SARS-CoV-2 in silico and evaluate their safety and efficacy in vitro and in vivo. METHOD The phytochemicals for anti-SARS-CoV-2 were screened in silico using molecular docking. The hits generated from in silico screening were subjected for extraction, isolation and purification. The anti-SARS-CoV-2 activity of Zanthoxylum piperitum (E1), Withania somnifera (E2), Calophyllum inophyllum (E3), Andrographis paniculata (E4), Centella asiatica (E5) ethanol extracts. The aerial parts were used for E1, E3, E4, E5 and root was used for E2. The in vitro safety and anti-SARS-CoV-2 activity of plant methanol extracts were performed in VeroE6 cells using Remdesivir as positive control. The acute and sub-acute toxicity study was performed in Wistar male and female rats. RESULTS The percentage of cell viability for E4, E5 and E2 treated VeroE6 cells were remarkably good on the 24th and 48th hour of treatment. The in vitro anti-SARS-CoV-2 activity of E4, E5 and E2 were significant for both E gene and N gene. The percentage of SARS-CoV-2 inhibition for E4 was better than Remdesivir. For E gene and N gene, Remdesivir showed IC50 of 0.15 µM and 0.11 µM respectively, For E gene and N gene, E4 showed IC50 of 1.18 µg and 1.16 µg respectively. Taking the clue from in vitro findings, the E4, E5 and E2 were combined (E 4.5.2) and evaluated for acute and sub-acute toxicity in Wistar male and female rats. No statistically significant difference in haematological, biochemical and histopathological parameters were noticed. CONCLUSION The study demonstrated the anti-SARS-CoV-2 activity in vitro and safety of plant extracts in both in vitro and in vivo experimental conditions.
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Affiliation(s)
- Damle Latha
- Computational Biology, Atrimed Biotech LLP, Banglore, 560100, India
| | | | - Ganju Shiban
- Atrimed Pharmaceuticals Pvt. Ltd, Banglore, 560001, India
| | - C Chandrashekar
- Computational Biology, Atrimed Biotech LLP, Banglore, 560100, India
| | - B R Bharath
- Computational Biology, Atrimed Biotech LLP, Banglore, 560100, India
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11
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Sharma V, Qayum A, K. Kapoor K, Mukherjee D, Singh SK, Dhar MK, Kaul S. Synthesis of 14-deoxy-benzylidene-8,17-epoxy-diene-andrographolide derivatives and evaluation of their anticancer activities. J INDIAN CHEM SOC 2022. [DOI: 10.1016/j.jics.2022.100490] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
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12
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Zhao Y, Roy S, Wang C, Goel A. A Combined Treatment with Berberine and Andrographis Exhibits Enhanced Anti-Cancer Activity through Suppression of DNA Replication in Colorectal Cancer. Pharmaceuticals (Basel) 2022; 15:262. [PMID: 35337060 PMCID: PMC8953248 DOI: 10.3390/ph15030262] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2022] [Revised: 02/18/2022] [Accepted: 02/19/2022] [Indexed: 12/13/2022] Open
Abstract
The high morbidity and mortality associated with colorectal cancer (CRC) are largely due to the invariable development of chemoresistance to classic chemotherapies, as well as intolerance to their significant toxicity. Many pharmaceutical formulations screened from natural plant extracts offer safe, inexpensive, and multi-target therapeutic options. In this study, we demonstrated that Berberis vulgaris L. (Berberine) and Andrographis paniculata (Burm. f.) Nees (Andrographis) extracts exerted their synergistic amplified anti-cancer effects by jointly inhibiting cell viability, suppressing colony formation, and inducing cell cycle arrest. Consistent with our in-vitro findings, the amplified synergistic anti-cancer effects were also observed in subcutaneous xenograft preclinical animal models, as well as patient-derived primary tumor organoids. To explore the molecular mechanisms underlying the amplified synergistic anti-cancer effects, RNA sequencing was performed to identify candidate pathways and genes. A transcriptome analysis revealed that DNA-replication-related genes, including FEN1, MCM7, PRIM1, MCM5, POLA1, MCM4, and PCNA, may be responsible for the enhanced anticancer effects of these two natural extracts. Taken together, our data revealed the powerful enhanced synergistic anti-CRC effects of berberine and Andrographis and provide evidence for the combinational targeting of DNA-replication-related genes as a promising new strategy for the therapeutic option in the management of CRC patients.
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Affiliation(s)
- Yinghui Zhao
- Department of Molecular Diagnostics and Experimental Therapeutics, Beckman Research Institute of City of Hope, Monrovia, CA 91010, USA; (Y.Z.); (S.R.)
- Department of Clinical Laboratory, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250033, China;
| | - Souvick Roy
- Department of Molecular Diagnostics and Experimental Therapeutics, Beckman Research Institute of City of Hope, Monrovia, CA 91010, USA; (Y.Z.); (S.R.)
| | - Chuanxin Wang
- Department of Clinical Laboratory, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250033, China;
- Shandong Engineering & Technology Research Center for Tumor Marker Detection, Jinan 250033, China
- Shandong Provincial Clinical Medicine Research Center for Clinical Laboratory, Jinan 250033, China
| | - Ajay Goel
- Department of Molecular Diagnostics and Experimental Therapeutics, Beckman Research Institute of City of Hope, Monrovia, CA 91010, USA; (Y.Z.); (S.R.)
- City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA
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13
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Pandey N, Jyoti, Singh M, Dwivedi P, Sahoo SC, Mishra BB. Click chemistry inspired synthesis of andrographolide triazolyl conjugates for effective fluorescent sensing of ferric ions. Nat Prod Res 2021; 36:5438-5448. [PMID: 34905436 DOI: 10.1080/14786419.2021.2013837] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
The naturally occurring compound andrographolide 1 was used as a substrate for the synthesis of a novel terminal alkyne 3 which on copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction with azides 4a-l, 7 and 9 furnished a series of regioselective andrographolide triazolyl conjugates 5a-l, 8 and 10, respectively. A free glycoconjugate 6 was also prepared by selective deprotection of compound 5i in good yield. All the compounds were characterized by absorbance, FT-IR, NMR, and HR-MS analyses. The triazolyl conjugate 8 was further investigated as a probe for selective detection of Fe3+ ion in matrix. The mode of attachment of Fe3+ ion to the compound 8 was established by absorbance, fluorescence, infrared (IR), and nuclear magnetic resonance (NMR) spectroscopy, and high resolution mass-spectrometry (HR-MS). The logic gate circuits were constructed for the probe 8 and ethylenediaminetetraacetic acid (EDTA). The environmental perspective of probe 8 was investigated in real water samples.
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Affiliation(s)
- Nishant Pandey
- Center of Innovative and Applied Bioprocessing (CIAB), Mohali, Punjab, India.,Department of Chemistry, Faculty of Science, Panjab University, Chandigarh, India
| | - Jyoti
- Center of Innovative and Applied Bioprocessing (CIAB), Mohali, Punjab, India.,Department of Chemistry, Faculty of Science, Panjab University, Chandigarh, India
| | - Mangat Singh
- Center of Innovative and Applied Bioprocessing (CIAB), Mohali, Punjab, India.,Department of Chemistry, Faculty of Science, Panjab University, Chandigarh, India
| | - Pratibha Dwivedi
- Center of Innovative and Applied Bioprocessing (CIAB), Mohali, Punjab, India
| | - Subash C Sahoo
- Department of Chemistry, Faculty of Science, Panjab University, Chandigarh, India
| | - Bhuwan B Mishra
- Center of Innovative and Applied Bioprocessing (CIAB), Mohali, Punjab, India
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14
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The Dietary Intake of Carrot-Derived Rhamnogalacturonan-I Accelerates and Augments the Innate Immune and Anti-Viral Interferon Response to Rhinovirus Infection and Reduces Duration and Severity of Symptoms in Humans in a Randomized Trial. Nutrients 2021; 13:nu13124395. [PMID: 34959949 PMCID: PMC8704532 DOI: 10.3390/nu13124395] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2021] [Revised: 11/25/2021] [Accepted: 12/01/2021] [Indexed: 12/12/2022] Open
Abstract
Acute respiratory infections are an important health concern. Traditionally, polysaccharide-enriched extracts from plants, containing immunomodulatory rhamnogalacturonan-I (RG-1), were used prophylactically. We established the effects of dietary supplementation with carrot-derived RG-I (cRG-I, 0–0.3–1.5 g/day) in 177 healthy individuals (18–65 years) on symptoms following infection with rhinovirus strain 16 (RV16). Primary outcomes were changes in severity and duration of symptoms, and viral load in nasal lavage. Secondary outcomes were changes in innate immune and anti-viral responses, reflected by CXCL10 and CXCL8 levels and cell differentials in nasal lavage. In a nested cohort, exploratory transcriptome analysis was conducted on nasal epithelium. Intake of cRG-I was safe, well-tolerated and accelerated local cellular and humoral innate immune responses induced by RV16 infection, with the strongest effects at 1.5 g/d. At 0.3 g/d, a faster interferon-induced response, induction of the key anti-viral gene EIF2AK2, faster viral clearance, and reduced symptom severity (−20%) and duration (−25%) were observed. Anti-viral responses, viral clearance and symptom scores at 1.5 g/d were in between those of 0 and 0.3 g/d, suggesting a negative feedback loop preventing excessive interferon responses. Dietary intake of cRG-I accelerated innate immune and antiviral responses, and reduced symptoms of an acute respiratory viral infection.
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Li X, Chen C, Leng A, Qu J. Advances in the Extraction, Purification, Structural Characteristics and Biological Activities of Eleutherococcus senticosus Polysaccharides: A Promising Medicinal and Edible Resource With Development Value. Front Pharmacol 2021; 12:753007. [PMID: 34790125 PMCID: PMC8591254 DOI: 10.3389/fphar.2021.753007] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2021] [Accepted: 10/04/2021] [Indexed: 11/29/2022] Open
Abstract
In recent years, natural polysaccharides have received growing attention and interest in view of their values in food, medical, cosmetics and other fields. Eleutherococcus senticosus (E. senticosus) is a medicine and food homologous plant that possess anti-tumor, anti-inflammatory, central nervous system and cardiovascular protection, anti-radiation, enhancement of human microcirculation, improvement of physical fatigue effects, mainly based on lignans, flavonoids and coumarin types. E. senticosus polysaccharides (ESPS), act as a kind of polysaccharide extracted and isolated from the root and rhizome of E. senticosus, have been found in many applications of medicine and food for their unique biological activity. Nevertheless, the existing studies are mostly concerned with small molecules of E. senticosus, less attention is paid to polysaccharides. Moreover, the types and structural characterization of ESPS reported in existing literature were also not summarized. In this paper, the research progress of ESPS is reviewed from the aspects of extraction, separation, structural characterization and biological activity, future perspectives from points of efficient extraction, resource utilization and quality control standards were also proposed, which provide reference for the further development and utilization of ESPS.
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Affiliation(s)
- Xiaojie Li
- Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, China.,Institute (College) of Pharmacy, Dalian Medical University, Dalian, China
| | - Cai Chen
- Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, China.,Institute (College) of Integrative Medicine, Dalian Medical University, Dalian, China
| | - Aijing Leng
- Institute (College) of Integrative Medicine, Dalian Medical University, Dalian, China.,Department of Traditional Chinese Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Jialin Qu
- Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, China.,Institute (College) of Integrative Medicine, Dalian Medical University, Dalian, China
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16
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Early intervention with Kan Jang® to treat upper-respiratory tract infections: A randomized, quadruple-blind study. J Tradit Complement Med 2021; 11:552-562. [PMID: 34765519 PMCID: PMC8572720 DOI: 10.1016/j.jtcme.2021.06.001] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2021] [Revised: 05/26/2021] [Accepted: 06/05/2021] [Indexed: 01/21/2023] Open
Abstract
Background and aim Andrographis paniculata and Eleutherococcus senticosus preparations and their fixed combination, called Kan Jang®, are traditionally used for relieving symptoms of upper-respiratory tract infections (URTIs). This study aimed to assess the efficacy of early intervention with Kan Jang® on the relief and duration of inflammatory symptoms during the acute phase of the disease. Experimental procedure A total of 179 patients with URTI symptoms received six Kan Jang® (daily dose of andrographolides: 60 mg) or placebo capsules a day for five consecutive days in this randomized, quadruple-blinded, placebo-controlled, two-parallel-group phase II study. The primary efficacy outcomes were the decrease in the acute-phase duration and the mean URTI symptoms score (sore throat, runny nose, nasal congestion, hoarseness, cough, headache, and fatigue). Results Early intervention with Kan Jang® significantly increased the recovery rate and reduced the number of sick leave days by >21% (0.64/day) relative to that observed in the placebo group (2.38 vs. 3.02 days, p = 0.0053). Kan Jang® significantly alleviated all URTI symptoms starting from the second day of treatment. A superior anti-inflammatory effect of Kan Jang® to that of placebo was also observed on the white blood cell count (p = 0.007) and erythrocyte sedimentation rate (p = 0.0258). Treatment with Kan Jang® was tolerated well. Conclusion This study demonstrates that early intervention with Kan Jang® capsules reduces the recovery duration of patients by 21% and significantly relieves the severity of typical URTI symptoms.
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Key Words
- Andrographis paniculata
- Clinical trial
- ESR, erythrocyte sedimentation rate
- Eleutherococcus senticosus
- FI, farb (colour) index
- GCP, good clinical practice
- GMP, good manufacturing practice
- ICH, international conference on harmonization
- Inflammation.
- Kan Jang®
- OR, odds ratio
- QP, qualified pharmacist
- RBC, red blood cell
- TSS, total symptom score
- URTI, upper respiratory tract infection
- Upper-respiratory tract infections
- VAS, visual analog scale
- WBC, white blood cell
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17
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Qian H, Yang H, Li X, Yang G, Zheng X, He T, Li S, Liu B, Wu Y, Cheng Y, Shen F. Andrographolide sulfonate attenuates alveolar hypercoagulation and fibrinolytic inhibition partly via NF-κB pathway in LPS-induced acute respiratory distress syndrome in mice. Biomed Pharmacother 2021; 143:112209. [PMID: 34649343 DOI: 10.1016/j.biopha.2021.112209] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2021] [Revised: 09/11/2021] [Accepted: 09/13/2021] [Indexed: 10/20/2022] Open
Abstract
BACKGROUND Alveolar hypercoagulation and fibrinolytic inhibition are important characteristics during acute respiratory distress syndrome (ARDS), and NF-κB p65 signaling pathway is involved to regulate these pathophysiologies. We hypothesize that targeting NF-κB signal pathway could ameliorate alveolar hypercoagulation and fibrinolyitc inhibition, thus attenuating lung injury in ARDS. PURPOSE We explore the efficacy and the potential mechanism of andrographolide sulfonate (Andro-S) on alveolar hypercoagulation and fibrinolytic inhibition in LPS-induced ARDS in mice. METHODS ARDS was made by lipopolysaccharide (LPS) inhalation in C57BLmice. Andrographolide sulfonate (2.5, 5 and 10 mg/kg) was intraperitoneally given to the mice (once a day for three consecutive days) before LPS administration. NEMO binding domain peptide (NBD), an inhibitor of NF-κB, was used as the positive control and it replaced Andro-S in mice of NBD group. Mice in normal control received saline instead of LPS. Lung tissues and bronchoalveolar lavage fluid (BALF) were collected for analysis of alveolar coagulation, fibrinolytic inhibition as well as of pulmonary inflammatory response after 8 h of LPS inhalation. NF-κB signal pathway in lung tissue was simultaneously determined. RESULTS Andro-S dose-dependently inhibited tissue factor (TF) and plasminogen activator inhibitor (PAI)-1 expressions either in mRNA or in protein in lung tissue of ARDS mice, and it also decreased the concentrations of TF, PAI-1, thrombin-antithrombin complex (TAT), procollagen peptide type Ⅲ (PⅢP) while promoting the production of activated protein C (APC) in BALF. Meanwhile, Andro-S effectively inhibited inflammatory response (interleukin 1β and myeloperoxidase) induced by LPS. LPS stimulation dramatically activated NF-κB signal pathway, indicated by increased expressions of phosphorylation of p65 (p-p65), p-IKKα/β and p-IκBα and the higher p65-DNA binding activity, which were all dose-dependently reversed by Andro-S. Andro-S and NBD presented similar efficacies. CONCLUSIONS Andro-S treatment improves alveolar hypercoagulation and fibrinolytic inhibition and attenuates pulmonary inflammation in LPS-induced ARDS in mice partly through NF-κB pathway inactivation. The drug is expected to be an effective choice for ARDS.
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Affiliation(s)
- Hong Qian
- Department of Intensive Care Unit, Guizhou Medical University Affiliated Hospital, Guiyang 550001, China; Department of Intensive Care Unit, The Second People's Hospital of Guiyang, 550001, China.
| | - Huilin Yang
- Department of Intensive Care Unit, Guizhou Medical University Affiliated Hospital, Guiyang 550001, China.
| | - Xiang Li
- Department of Intensive Care Unit, Guizhou Medical University Affiliated Hospital, Guiyang 550001, China.
| | - Guixia Yang
- Department of Intensive Care Unit, Guizhou Medical University Affiliated Hospital, Guiyang 550001, China.
| | - Xinghao Zheng
- Department of Intensive Care Unit, Guizhou Medical University Affiliated Hospital, Guiyang 550001, China.
| | - Tianhui He
- Department of Intensive Care Unit, Guizhou Medical University Affiliated Hospital, Guiyang 550001, China.
| | - Shuwen Li
- Department of Intensive Care Unit, Guizhou Medical University Affiliated Hospital, Guiyang 550001, China.
| | - Bo Liu
- Department of Intensive Care Unit, Guizhou Medical University Affiliated Hospital, Guiyang 550001, China.
| | - Yanqi Wu
- Department of Intensive Care Unit, Guizhou Medical University Affiliated Hospital, Guiyang 550001, China.
| | - Yumei Cheng
- Department of Intensive Care Unit, Guizhou Medical University Affiliated Hospital, Guiyang 550001, China.
| | - Feng Shen
- Department of Intensive Care Unit, Guizhou Medical University Affiliated Hospital, Guiyang 550001, China.
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18
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Gupta S, Mishra KP, Gupta R, Singh SB. Andrographolide - A prospective remedy for chikungunya fever and viral arthritis. Int Immunopharmacol 2021; 99:108045. [PMID: 34435582 DOI: 10.1016/j.intimp.2021.108045] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2021] [Revised: 08/01/2021] [Accepted: 08/01/2021] [Indexed: 12/14/2022]
Abstract
AIM Andrographolide, the major bioactive compound of the plant Andrographis paniculata, exerts anti-inflammatory, cyto-, neuro- and hepato-protective effects. Traditional remedies for infectious diseases include A. paniculata for maladies like fever, pain, rashes which are associated with chikungunya and other arboviral diseases. Since andrographolide and A. paniculata have potent antiviral properties, the present review aims to provide a comprehensive report of symptoms and immunological molecules involved in chikungunya virus (CHIKV) infection and the therapeutic role of andrographolide in the mitigation of chikungunya and associated symptoms. MATERIALS AND METHODS Studies on the therapeutic role of A. paniculata and andrographolide in chikungunya and other viral infections published between 1991 and 2021 were searched on various databases. RESULTS AND DISCUSSION The havoc created by chikungunya is due to the associated debilitating symptoms including arthralgia and myalgia which sometimes remains for years. The authors reviewed and summarized the various symptoms and immunological molecules related to CHIKV replication and associated inflammation, oxidative and unfolded protein stress, apoptosis and arthritis. Additionally, the authors suggested andrographolide as a remedy for chikungunya and other arboviral infections by highlighting its role in the regulation of molecules involved in unfolded protein response pathway, immunomodulation, inflammation, virus multiplication, oxidative stress, apoptosis and arthritis. CONCLUSION The present review demonstrated the major complications associated with chikungunya and the role of andrographolide in alleviating the chikungunya associated symptoms to encourage further investigations using this promising compound towards early development of an anti-CHIKV drug. Chemical Compound studied: andrographolide (PubChem CID: 5318517).
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Affiliation(s)
- Swati Gupta
- Division of Epidemiology and Communicable Diseases, Indian Council of Medical Research (ICMR), Ansari Nagar, New Delhi 110029, India.
| | - K P Mishra
- Defence Research and Development Organization (DRDO)-HQ, Rajaji Marg, New Delhi 110011, India
| | - Rupali Gupta
- Department of Neurology, Duke University Medical Center, Durham, NC, United States
| | - S B Singh
- National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, India
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Li W, Pan B, Shi Y, Wang M, Han T, Wang Q, Duan G, Fu H. Identification of poly(ADP-ribose)polymerase 1 and 2 (PARP1/2) as targets of andrographolide using an integrated chemical biology approach. Chem Commun (Camb) 2021; 57:6308-6311. [PMID: 34075974 DOI: 10.1039/d1cc02272e] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Here, we describe the identification of PARP1/2 as direct binding proteins of andrographolide (Andro) using protein microarray, surface plasmon resonance (SPR), and enzyme activity assays. We then evaluated the proliferation inhibition, apoptosis, and cell migration effects of Andro on the MDA-MB-436 cell line in vitro. The final biological evaluation confirmed that Andro was a highly effective single agent in the MDA-MB-436 xenograft model and had a low hERG-mediated cardiac toxicity. Therefore, Andro represents the first natural product, non-amide member of a novel nanomolar-potency PARP1/2 inhibitor family.
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Affiliation(s)
- Wenchao Li
- State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, People's Republic of China.
| | - Bowen Pan
- State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, People's Republic of China. and College of Pharmacy, Guizhou University of Traditional Chinese Medicine, Guiyang 550025, People's Republic of China
| | - Yang Shi
- State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, People's Republic of China. and College of Pharmacy, Guizhou University of Traditional Chinese Medicine, Guiyang 550025, People's Republic of China
| | - Meiying Wang
- State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, People's Republic of China.
| | - Tianjiao Han
- State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, People's Republic of China.
| | - Qing Wang
- State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, People's Republic of China.
| | - Guifang Duan
- State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, People's Republic of China.
| | - Hongzheng Fu
- State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, People's Republic of China.
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Kumar S, Singh B, Bajpai V. Andrographis paniculata (Burm.f.) Nees: Traditional uses, phytochemistry, pharmacological properties and quality control/quality assurance. JOURNAL OF ETHNOPHARMACOLOGY 2021; 275:114054. [PMID: 33831465 DOI: 10.1016/j.jep.2021.114054] [Citation(s) in RCA: 69] [Impact Index Per Article: 17.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/25/2020] [Revised: 01/22/2021] [Accepted: 03/16/2021] [Indexed: 06/12/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Andrographis paniculata (Burm.f.) Nees is a medicinal herb of the Asian countries used in many traditional medicinal systems for the treatment of diarrhea, flu, leprosy, leptospirosis, malaria, rabies, upper respiratory infections, sinusitis, syphilis, tuberculosis and HIV/AIDS etc. AIM OF THE STUDY: This review aims to provide the comprehensive, accurate and authentic information on traditional uses, phytochemistry and pharmacological properties of various extracts/fractions as well as phytocostituents of A. paniculata. In addition, this review also aims to provide advance and sensitive analytical methods along with chemical markers used in the standardization of herbal products for quality control (QC)/quality assurance (QA). MATERIALS AND METHODS All relevant publications were considered within the years 1983-2020. The publications were searched from Google Scholar, PubChem, Chemspider, PubMed, Elsevier, Wiley, Web of Science, China Knowledge Resource Integrated databases and ResearchGate using a combination of various relevant keywords. Besides, relevant published books and chapters were also considered those providing an overview of extant secondary literature related to traditional knowledge, phytochemistry, pharmacology and toxicity of the plant. RESULTS AND DISCUSSION In this review, 344 compounds, including, terpenoid lactones, flavonoids, phenolic acids, triterpenes and volatile compounds were summarized out of which more than half of the compounds have no reported pharmacological activities yet. Terpenoid lactones and flavonoids are the major bioactive classes of compounds of A. paniculata which are responsible for pharmacological activities such as anticancer and antioxidant activities, respectively. Biosynthetic pathways and active sites for target proteins of both terpenoid lactones and flavonoids were considered. Analgesic, anticancer, antidiabetic, antifertility, antiinflammatory, antimalarial, antimicrobial, antioxidant, antipyretic, antiviral, antiretroviral, antivenom, cardioprotective, hepatoprotective, immunomodulatory and neuroprotective activities have been also reported. Andrographolide is a major characteristic active principle and responsible for most of the pharmacological activities. Therefore, andrographolide has been selected as a marker for the standardization of raw and marketed herbal products by TLC, HPTLC, HPLC, GC-MS, HPLC-MS and HPLC-MS/MS methods for QC/QA. CONCLUSIONS Conclusive evidence showed that the pharmacological activities reported in crude extracts and chemical markers are supporting and provides confidence in the traditional use of A. paniculata as a herbal medicine. The andrographolide could be used as a chemical marker for the QC/QA of raw and A. paniculata derived herbal products. Lactone ring in terpenoid lactone is an active site for targeted proteins. More efforts should be focused on the identification of the chemical markers from A. paniculata to provide a practical basis for QC/QA. Several aspects such as the mechanism of therapeutic potential, molecular docking technology and multi-target network pharmacology are very important for drug discovery and needed more investigation and should be considered. This compilation may be helpful in further study and QC/QA.
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Affiliation(s)
- Sunil Kumar
- Department of Chemistry, Ma. Kanshiram Government Degree College, Ninowa, Farrukhabad, 209602, India(1).
| | - Bikarma Singh
- Botanic Garden Division, CSIR- National Botanical Research Institute (NBRI), Lucknow, 226001, Uttar Pradesh, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India.
| | - Vikas Bajpai
- Sophisticated Analytical Instrument Facility, CSIR-Central Drug Research Institute, Lucknow, 226031, Uttar Pradesh, India.
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21
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Banerjee S, Kar A, Mukherjee PK, Haldar PK, Sharma N, Katiyar CK. Immunoprotective potential of Ayurvedic herb Kalmegh (Andrographis paniculata) against respiratory viral infections - LC-MS/MS and network pharmacology analysis. PHYTOCHEMICAL ANALYSIS : PCA 2021; 32:629-639. [PMID: 33167083 DOI: 10.1002/pca.3011] [Citation(s) in RCA: 38] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/01/2020] [Revised: 10/05/2020] [Accepted: 10/07/2020] [Indexed: 05/04/2023]
Abstract
INTRODUCTION Immunity boosting has emerged as a global strategy to fight the SARS-CoV-2 pandemic situation. In India, AYUSH systems of medicine have been promoted as an immune-protection strategy. Andrographis paniculata (Burm. F) Nees (AP) mentioned in Ayurveda has been widely used for treating sore throat, flu, and upper respiratory tract infections which may provide possible novel therapeutic approaches, exclusively targeting SARS-CoV-2 and its pathways. OBJECTIVES The present work uses liquid chromatography-tandem mass spectrometry (LC-MS/MS) metabolomics and combination synergy analysis based on network pharmacology to mine multimode evidence to understand the possible mechanism of action, diseases association, protein-protein interaction and major pathways involved therein. MATERIAL AND METHODS Metabolite profiling was performed by Agilent QTOF LC-MS/MS system. Network pharmacology analysis was performed by using functional annotation analysis based on databases like Binding DB, STRING, DAVID and KEGG for further data mining. Further combination synergy was evaluated using "neighbourhood approach" and networks were constructed through Cytoscape 3.2.1. RESULTS The molecules from kalmegh provides immune-protection and anti-viral response via involving different pathways, like toll-like receptor pathway, PI3/AKT pathway and MAP kinase pathways against COVID-19 infection. The KEGG analysis showed that in a vast majority of the most enriched pathways, AP were associated with viral infections and upper respiratory tract infections. CONCLUSIONS The results suggest a synergy between andrographolide and other molecules identified as safe and efficacious anti-inflammatory agent having effects on upper respiratory tract infections and can significantly decrease the production of cytokines and pro-inflammatory factors in viral infections.
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Affiliation(s)
- Subhadip Banerjee
- School of Natural Product Studies, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, India
| | - Amit Kar
- School of Natural Product Studies, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, India
| | - Pulok K Mukherjee
- School of Natural Product Studies, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, India
- Institute of Bioresources and Sustainable Development, An Autonomous Institute under Department of Biotechnology, Government of India, Imphal, India
| | - Pallab K Haldar
- School of Natural Product Studies, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, India
| | - Nanaocha Sharma
- Institute of Bioresources and Sustainable Development, An Autonomous Institute under Department of Biotechnology, Government of India, Imphal, India
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22
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Ma R, Shimura T, Yin C, Okugawa Y, Kitajima T, Koike Y, Okita Y, Ohi M, Uchida K, Goel A, Yao L, Zhang X, Toiyama Y. Antitumor effects of Andrographis via ferroptosis-associated genes in gastric cancer. Oncol Lett 2021; 22:523. [PMID: 34025790 DOI: 10.3892/ol.2021.12784] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2021] [Accepted: 03/31/2021] [Indexed: 12/24/2022] Open
Abstract
The overall prognosis of advanced/metastatic gastric cancer (GC) remains poor despite the development of pharmacotherapy. Therefore, other treatment options, such as complementary and alternative medicine, should be considered to overcome this aggressive malignancy. Andrographis, which is a generally unharmful botanical compound, has gained increasing interest for its anticancer effects in multiple malignancies via the regulation of cancer progression-associated signaling pathways. In the present study, a series of in vitro experiments (cell proliferation, colony formation and apoptosis assays) was designed to elucidate the antitumor potential and mechanism of Andrographis in GC cells. The present study demonstrated that Andrographis exerted antitumor effects in GC cell lines (MKN74 and NUGC4) by inhibiting proliferation, reducing colony formation and enhancing apoptotic activity. Furthermore, it was demonstrated that the expression levels of the ferroptosis-associated genes heme oxygenase-1, glutamate-cysteine ligase catalytic and glutamate-cysteine ligase modifier were significantly upregulated after Andrographis treatment in both GC cell lines in reverse transcription-quantitative PCR experiments (P<0.05); this finding was further confirmed by immunoblotting assays (P<0.05). In conclusion, to the best of our knowledge, the present study was the first to demonstrate that Andrographis possessed antitumor properties by altering the expression levels of ferroptosis-associated genes, thereby providing novel insights into the potential of Andrographis as an adjunctive treatment option for patients with metastatic GC.
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Affiliation(s)
- Ruiya Ma
- Department of Gastrointestinal and Pediatric Surgery, Institute of Life Sciences, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, Japan.,Department of Colorectal Surgery, Tangshan Gongren Hospital, Tangshan, Hebei 063000, P.R. China
| | - Tadanobu Shimura
- Department of Gastrointestinal and Pediatric Surgery, Institute of Life Sciences, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, Japan
| | - Chengzeng Yin
- Department of Gastrointestinal and Pediatric Surgery, Institute of Life Sciences, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, Japan
| | - Yoshinaga Okugawa
- Department of Genomic Medicine, Mie University Hospital, Tsu, Mie 514-8507, Japan
| | - Takahito Kitajima
- Department of Gastrointestinal and Pediatric Surgery, Institute of Life Sciences, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, Japan
| | - Yuhki Koike
- Department of Gastrointestinal and Pediatric Surgery, Institute of Life Sciences, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, Japan
| | - Yoshiki Okita
- Department of Gastrointestinal and Pediatric Surgery, Institute of Life Sciences, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, Japan
| | - Masaki Ohi
- Department of Gastrointestinal and Pediatric Surgery, Institute of Life Sciences, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, Japan
| | - Keiichi Uchida
- Department of Gastrointestinal and Pediatric Surgery, Institute of Life Sciences, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, Japan
| | - Ajay Goel
- Department of Molecular Diagnostics and Experimental Therapeutics, Beckman Research Institute, City of Hope Comprehensive Cancer Center, Duarte, CA 91016, USA
| | - Li Yao
- Department of Surgery, China-Japan Friendship Hospital, Beijing 100029, P.R. China
| | - Xueming Zhang
- Department of Colorectal Surgery, Tangshan Gongren Hospital, Tangshan, Hebei 063000, P.R. China
| | - Yuji Toiyama
- Department of Gastrointestinal and Pediatric Surgery, Institute of Life Sciences, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, Japan
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23
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Hossain S, Urbi Z, Karuniawati H, Mohiuddin RB, Moh Qrimida A, Allzrag AMM, Ming LC, Pagano E, Capasso R. Andrographis paniculata (Burm. f.) Wall. ex Nees: An Updated Review of Phytochemistry, Antimicrobial Pharmacology, and Clinical Safety and Efficacy. Life (Basel) 2021; 11:348. [PMID: 33923529 PMCID: PMC8072717 DOI: 10.3390/life11040348] [Citation(s) in RCA: 96] [Impact Index Per Article: 24.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2021] [Revised: 04/02/2021] [Accepted: 04/03/2021] [Indexed: 02/07/2023] Open
Abstract
Infectious disease (ID) is one of the top-most serious threats to human health globally, further aggravated by antimicrobial resistance and lack of novel immunization options. Andrographis paniculata (Burm. f.) Wall. ex Nees and its metabolites have been long used to treat IDs. Andrographolide, derived from A. paniculata, can inhibit invasive microbes virulence factors and regulate the host immunity. Controlled clinical trials revealed that A. paniculata treatment is safe and efficacious for acute respiratory tract infections like common cold and sinusitis. Hence, A. paniculata, mainly andrographolide, could be considered as an excellent candidate for antimicrobial drug development. Considering the importance, medicinal values, and significant role as antimicrobial agents, this study critically evaluated the antimicrobial therapeutic potency of A. paniculata and its metabolites, focusing on the mechanism of action in inhibiting invasive microbes and biofilm formation. A critical evaluation of the secondary metabolites with the aim of identifying pure compounds that possess antimicrobial functions has further added significant values to this study. Notwithstanding that A. paniculata is a promising source of antimicrobial agents and safe treatment for IDs, further empirical research is warranted.
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Affiliation(s)
- Sanower Hossain
- Department of Biomedical Science, Kulliyyah of Allied Health Sciences, International Islamic University Malaysia, Kuantan 25200, Pahang, Malaysia
| | - Zannat Urbi
- Department of Industrial Biotechnology, Faculty of Industrial Sciences & Technology, Universiti Malaysia Pahang, Kuantan 26300, Pahang, Malaysia;
| | - Hidayah Karuniawati
- Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Muhammadiyah Surakarta, Surakarta 57102, Indonesia;
| | - Ramisa Binti Mohiuddin
- Department of Pharmacy, Faculty of Life Science, Mawlana Bhashani Science and Technology University, Santosh 1902, Tangail, Bangladesh;
| | - Ahmed Moh Qrimida
- Department of Agriculture, Higher Institute of Overall Occupations-Sooq Al Khamees Imsahil, Tripoli 1300, Libya; (A.M.Q.); (A.M.M.A.)
| | - Akrm Mohamed Masaud Allzrag
- Department of Agriculture, Higher Institute of Overall Occupations-Sooq Al Khamees Imsahil, Tripoli 1300, Libya; (A.M.Q.); (A.M.M.A.)
| | - Long Chiau Ming
- PAP Rashidah Sa’adatul Bolkiah Institute of Health Sciences, Universiti Brunei Darussalam, Jalan Tungku Link, Gadong BE1410, Brunei;
| | - Ester Pagano
- Department of Pharmacy, University of Naples Federico II, 80131 Naples, Italy;
| | - Raffaele Capasso
- Department of Agricultural Sciences, University of Naples Federico II, 80055 Portici, Italy
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24
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Shimura T, Sharma P, Sharma GG, Banwait JK, Goel A. Enhanced anti-cancer activity of andrographis with oligomeric proanthocyanidins through activation of metabolic and ferroptosis pathways in colorectal cancer. Sci Rep 2021; 11:7548. [PMID: 33824419 PMCID: PMC8024269 DOI: 10.1038/s41598-021-87283-y] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2020] [Accepted: 03/22/2021] [Indexed: 01/14/2023] Open
Abstract
The high degree of morbidity and mortality in colorectal cancer (CRC) patients is largely due to the development of chemoresistance against conventional chemotherapeutic drugs. In view of the accumulating evidence that various dietary botanicals offer a safe, inexpensive and multi-targeted treatment option, herein, we hypothesized that a combination of Andrographis paniculata and Oligomeric Proanthocyanidins (OPCs) might interact together with regard to anti-tumorigenic activity in CRC. As a result, we demonstrated the enhanced anti-cancer activity between these two botanical extracts in terms of their ability to inhibit cancer cell growth, suppress colony formation and induce apoptosis. Furthermore, we validated these findings in subcutaneous xenograft model and in patient derived primary epithelial 3D organoids. Transcriptomic profiling identified involvement of metabolic pathways and ferroptosis-associated genes, including HMOX1, GCLC and GCLM, that may be responsible for the increased anti-tumorigenic activity by the two compounds. Collectively, our study provides novel evidence in support of the combinatorial use of andrographis and OPCs as a potential therapeutic option, perhaps as an adjunctive treatment to classical drugs, in patients with colorectal cancer.
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Affiliation(s)
- Tadanobu Shimura
- Center for Gastrointestinal Research, Baylor Scott & White Research Institute and Charles A. Sammons Cancer Center, Baylor University Medical Center, Dallas, TX, USA
| | - Priyanka Sharma
- Center for Gastrointestinal Research, Baylor Scott & White Research Institute and Charles A. Sammons Cancer Center, Baylor University Medical Center, Dallas, TX, USA
- Department of Molecular Diagnostics and Experimental Therapeutics, Beckman Research Institute, City of Hope Comprehensive Cancer Center, Duarte, CA, USA
| | - Geeta G Sharma
- Department of Molecular Diagnostics and Experimental Therapeutics, Beckman Research Institute, City of Hope Comprehensive Cancer Center, Duarte, CA, USA
| | - Jasjit K Banwait
- Center for Gastrointestinal Research, Baylor Scott & White Research Institute and Charles A. Sammons Cancer Center, Baylor University Medical Center, Dallas, TX, USA
| | - Ajay Goel
- Center for Gastrointestinal Research, Baylor Scott & White Research Institute and Charles A. Sammons Cancer Center, Baylor University Medical Center, Dallas, TX, USA.
- Department of Molecular Diagnostics and Experimental Therapeutics, Beckman Research Institute, City of Hope Comprehensive Cancer Center, Duarte, CA, USA.
- Department of Molecular Diagnostics and Experimental Therapeutics, Biotech Innovations, Beckman Research Institute, City of Hope Comprehensive Cancer Center, 1218 S. Fifth Avenue, Suite 2226, Monrovia, CA, 91016, USA.
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25
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McKay S, Oranje P, Helin J, Koek JH, Kreijveld E, van den Abbeele P, Pohl U, Bothe G, Tzoumaki M, Aparicio-Vergara M, Mercenier A, Schols H, Albers R. Development of an Affordable, Sustainable and Efficacious Plant-Based Immunomodulatory Food Ingredient Based on Bell Pepper or Carrot RG-I Pectic Polysaccharides. Nutrients 2021; 13:nu13030963. [PMID: 33809720 PMCID: PMC8002328 DOI: 10.3390/nu13030963] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2021] [Revised: 03/10/2021] [Accepted: 03/12/2021] [Indexed: 12/18/2022] Open
Abstract
The prevalence of acute respiratory infections and their impact on quality of life underlies the need for efficacious solutions that are safe, sustainable and economically viable. Polysaccharides in several (traditional) plant extracts have been shown to be immunostimulatory, and some studies suggest beneficial effects against respiratory infections. The aim of this study was to (i) identify the active polysaccharide constituents from affordable and renewable crops (bell pepper and carrot) using activity-guided fractionation, (ii) evaluate in vitro effects on innate immune responses (phagocytosis and cytokine secretion), microbiota modulation and production of short chain fatty acids, followed by (iii) the evaluation of effects of a bell pepper extract enriched for the active component in a human proof of concept study. We identified rhamnogalacturonan-I (RG-I) as the nutricophore responsible for the immunostimulatory activity with substantial structural and functional equivalence between bell pepper (bp) and carrot (c). The in vitro studies showed that bpRG-I and cRG-I comprise similar immune- and microbiota modulatory potential and the human study demonstrated that bpRG-I was well tolerated and enhanced innate immune responsiveness in vivo. This is an important step towards testing the efficacy of RG-I from bpRG-I or cRG-I in an infection trial in humans.
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Affiliation(s)
- Sue McKay
- Suze Consulting, Voorweg 65, 3233 SJ Oostvoorne, The Netherlands;
| | - Paul Oranje
- IMcoMET BV, Marconistraat 16, 3029 AK Rotterdam, The Netherlands;
| | - Jari Helin
- Glykos Finland Oy, Viikinkaari 6, FI-00790 Helsinki, Finland;
| | - Jean H. Koek
- Unilever, Foods Innovation Centre, Bronland 14, 6708 WH Wageningen, The Netherlands;
| | - Ellen Kreijveld
- Rijk Zwaan, Burgemeester Crezéelaan 40, P.O. Box 40, 2678 KX De Lier, The Netherlands;
| | | | - Ute Pohl
- Analyze & Realize GmbH, Waldseeweg 6, 13467 Berlin, Germany; (U.P.); (G.B.)
| | - Gordana Bothe
- Analyze & Realize GmbH, Waldseeweg 6, 13467 Berlin, Germany; (U.P.); (G.B.)
| | - Maria Tzoumaki
- Nutrileads BV, Bronland 12-N, 6708 WH Wageningen, The Netherlands; (M.T.); (M.A.-V.); (A.M.)
| | | | - Annick Mercenier
- Nutrileads BV, Bronland 12-N, 6708 WH Wageningen, The Netherlands; (M.T.); (M.A.-V.); (A.M.)
| | - Henk Schols
- Laboratory of Food Chemistry, Wageningen University, Bornse Weilanden 9, 6708 WG Wageningen, The Netherlands;
| | - Ruud Albers
- Nutrileads BV, Bronland 12-N, 6708 WH Wageningen, The Netherlands; (M.T.); (M.A.-V.); (A.M.)
- Correspondence:
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26
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Peterson CT, Iablokov SN, Uchitel S, Chopra D, Perez-Santiago J, Rodionov DA, Peterson SN. Community Metabolic Interactions, Vitamin Production and Prebiotic Potential of Medicinal Herbs Used for Immunomodulation. Front Genet 2021; 12:584197. [PMID: 33613632 PMCID: PMC7886795 DOI: 10.3389/fgene.2021.584197] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2020] [Accepted: 01/13/2021] [Indexed: 12/12/2022] Open
Abstract
Historically, the health benefits and immunomodulatory potential of medicinal herbs have been considered an intrinsic quality of the herb itself. We have hypothesized that the health benefits of medicinal herbs may be partially due to their prebiotic potential that alter gut microbiota leading to changes in short chain fatty acids and vitamin production or biotransformation of herb encoded molecules and secondary metabolites. Accumulating studies emphasize the relationship between the gut microbiota and host immune function. While largely unknown, these interactions are mediated by secreted microbial products that activate or repress a variety of immune cell types. Here we evaluated the effect of immunomodulatory, medicinal Ayurvedic herbs on gut microbiota in vitro using 16S rRNA sequencing to assess changes in community composition and functional potential. All immunomodulatory herbs displayed substantial prebiotic potential, targeting unique taxonomic groups. Application of genome reconstruction and analysis of biosynthetic capacity of herb selected communities suggests that many of the 11 herbs tested altered the community metabolism as the result of differential glycan harvest and sugar utilization and secreted products including multiple vitamins, butyrate, and propionate that may impact host physiology and immune function. Taken together, these results provide a useful framework for the further evaluation of these immunomodulatory herbs in vivo to maintain immune homeostasis or achieve desired regulation of immune components in the context of disease.
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Affiliation(s)
- Christine T Peterson
- Department of Family Medicine and Public Health, Center of Excellence for Research and Training in Integrative Health, School of Medicine, University of California, San Diego, La Jolla, CA, United States
| | - Stanislav N Iablokov
- A.A. Kharkevich Institute for Information Transmission Problems, Russian Academy of Sciences, Moscow, Russia.,Department of Theoretical Physics, P.G. Demidov Yaroslavl State University, Yaroslavl, Russia
| | - Sasha Uchitel
- Department of Biology, Washington University, St. Louis, MO, United States
| | - Deepak Chopra
- Department of Family Medicine and Public Health, Center of Excellence for Research and Training in Integrative Health, School of Medicine, University of California, San Diego, La Jolla, CA, United States.,Department of Ayurveda and Yoga Research, Chopra Foundation, Carlsbad, CA, United States
| | - Josue Perez-Santiago
- Puerto Rico Omic Center Genomics Core Division of Cancer Biology, University of Puerto Rico Comprehensive Cancer Center, San Juan, Puerto Rico
| | - Dmitry A Rodionov
- A.A. Kharkevich Institute for Information Transmission Problems, Russian Academy of Sciences, Moscow, Russia.,Bioinformatics and Structural Biology Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, United States
| | - Scott N Peterson
- Puerto Rico Omic Center Genomics Core Division of Cancer Biology, University of Puerto Rico Comprehensive Cancer Center, San Juan, Puerto Rico.,Bioinformatics and Structural Biology Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, United States
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27
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Worakunphanich W, Thavorncharoensap M, Youngkong S, Thadanipon K, Thakkinstian A. Safety of Andrographis paniculata: A systematic review and meta-analysis. Pharmacoepidemiol Drug Saf 2021; 30:727-739. [PMID: 33372366 DOI: 10.1002/pds.5190] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2020] [Accepted: 12/17/2020] [Indexed: 11/11/2022]
Abstract
PURPOSE Andrographis paniculata is one of the commonly used herbal medicines worldwide. Nevertheless, evidences on adverse events (AEs) associated with Andrographis paniculata are very limited. This systematic review and meta-analysis was conducted to estimate and to compare the AE incidence of oral monotherapy Andrographis paniculata with others among patients with upper respiratory tract infection, noninfective diarrhea, and autoimmune disease. METHODS Systematic search was performed through six databases from inception until August 2018. Randomized controlled trial (RCT), cohort, or intensive monitoring of AEs was eligible for review if AE incidence was examined. The incidence of AEs was, then, pooled across studies using meta-analysis. RESULTS Ten RCTs and 3 intensive monitoring studies were included. Incidence of serious AEs was very rare with the pooled incidence (95% CI) from RCTs of 0.02 per 1000 patients (0.0-0.5). However, the incidence of nonserious AEs was considered very common with the pooled incidence (95% CI) from RCTs of 102.6 per 1000 patients (10.7-256.1), and the pooled incidence (95% CI) from intensive monitoring of 34.2 per 1000 patients (0.0-229.6). The most common nonserious AEs were related to gastrointestinal disorder, and skin and subcutaneous disorder system. CONCLUSIONS Like other medicine, Andrographis paniculata can cause some AEs. However, it may be generally safe. Nevertheless, prospective patients who plan to use Andrographis paniculata should be thoroughly advised and closely monitored for common AEs. Due to the increasing use of Andrographis paniculata worldwide, larger studies with adequate methodological quality are warranted to monitor the safety of such product.
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Affiliation(s)
- Wiwan Worakunphanich
- Doctor of Philosophy Program in Social, Economic, and Administrative Pharmacy, Department of Pharmacy, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand.,Thai Traditional Medicine Research Institute, Department of Thai Traditional and Alternative Medicine, Ministry of Public Health, Nonthaburi, Thailand
| | - Montarat Thavorncharoensap
- Health Technology Assessment Graduate Program, Mahidol University, Bangkok, Thailand.,Social and Administrative Pharmacy Excellence Research (SAPER) unit, Department of Pharmacy, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand
| | - Sitaporn Youngkong
- Health Technology Assessment Graduate Program, Mahidol University, Bangkok, Thailand.,Social and Administrative Pharmacy Excellence Research (SAPER) unit, Department of Pharmacy, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand
| | - Kunlawat Thadanipon
- Department of Clinical Epidemiology and Biostatistics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
| | - Ammarin Thakkinstian
- Health Technology Assessment Graduate Program, Mahidol University, Bangkok, Thailand.,Department of Clinical Epidemiology and Biostatistics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
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28
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Jalali A, Dabaghian F, Akbrialiabad H, Foroughinia F, Zarshenas MM. A pharmacology-based comprehensive review on medicinal plants and phytoactive constituents possibly effective in the management of COVID-19. Phytother Res 2020; 35:1925-1938. [PMID: 33159391 DOI: 10.1002/ptr.6936] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2020] [Revised: 09/18/2020] [Accepted: 10/18/2020] [Indexed: 12/15/2022]
Abstract
Arisen in China, COVID-19 (SARS-CoV-II) is a novel coronavirus that has been expanding fast worldwide. Till now, no definite remedial drug or vaccine has been identified for COVID-19 treatment. Still, for a majority of infected patients, supportive therapy is the cornerstone of the management plan. To the importance of managing the COVID-19 pandemic, this article proposed to collecting capable medicinal plants and bioactive components in both treat and supportive therapy of this novel viral infection. Clinical points in the pathogenesis, symptoms, and complications of COVID-19 were considered. The effective plants and bioactives that may play a role in supportive therapy/management of COVID-19 were searched, collected through the "Scopus" database and listed in three sections. Numerous medicinal plants such as Citrus Spp., Camellia sinensis, and Glycyrrhiza glabra can interference with COVID-19 pathogenesis via inhibition of virus replication and entry to its host cells. Also, some anti-inflammatory herbal medicine such as Andrographis paniculata, Citrus spp., and Cuminum cyminum can relieve fever and cough in COVID-19 patients. Medicinal plants such as G. glabra, Thymus vulgaris, Allium sativum, Althea officinalis, and Panax ginseng may modulate the immune system and possess prevention and supportive therapy. However, more clinical data are required to confirm these hypotheses.
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Affiliation(s)
- Atefeh Jalali
- Medicinal Plants Processing Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.,Department of Phytopharmaceuticals (Traditional Pharmacy), School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Farid Dabaghian
- Department of Pharmacognosy, School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| | - Hossein Akbrialiabad
- Medicinal Plants Processing Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.,Student Research Committee, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Farzaneh Foroughinia
- Department of Clinical Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mohammad M Zarshenas
- Medicinal Plants Processing Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.,Department of Phytopharmaceuticals (Traditional Pharmacy), School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.,Epilepsy Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
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29
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Jia Y, Zhang H, Yang S, Xi Z, Tang T, Yin R, Zhang W. Electrospun PLGA membrane incorporated with andrographolide-loaded mesoporous silica nanoparticles for sustained antibacterial wound dressing. Nanomedicine (Lond) 2018; 13:2881-2899. [DOI: 10.2217/nnm-2018-0099] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
Aim: To assess the wound-healing ability of poly(lactic-co-glycolic acid) (PLGA) nanofibrous wound dressing incorporated with andrographolide (Andro)-loaded mesoporous silica nanoparticles (MSNs). Materials & methods: PLGA/Andro-MSNs nanofibrous membrane wound dressings were produced by electrospinning. The effects of MSNs on the hydrophilicity, degradation and mechanical strength of membranes were evaluated. The cumulative release of Andro in vitro was obtained. Cell culture and in vivo tests on infectious models were carried out. Results: The PLGA/Andro-MSNs membrane showed a sustained release of Andro. The incorporation of MSNs into PLGA improved the hydrophilicity of the nanofibrous membranes. Cell culture and in vivo tests showed that PLGA/Andro-MSNs membrane can promote epidermal cell adhesion and reduce inflammation process. Conclusion: PLGA/Andro-MSNs nanofibrous membrane exhibited an efficient wound-healing ability.
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Affiliation(s)
- Yuhang Jia
- School of Mechanical & Power Engineering, Complex and Intelligent Systems Research Centre, East China University of Science & Technology, Shanghai 200237, China
| | - Hongbo Zhang
- School of Mechanical & Power Engineering, Complex and Intelligent Systems Research Centre, East China University of Science & Technology, Shanghai 200237, China
| | - Shengbing Yang
- Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China
| | - Zhenhao Xi
- School of Chemical Engineering, East China University of Science & Technology, Shanghai 200237, China
| | - Tingting Tang
- Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China
| | - Ruixue Yin
- School of Mechanical & Power Engineering, Complex and Intelligent Systems Research Centre, East China University of Science & Technology, Shanghai 200237, China
| | - Wenjun Zhang
- Division of Biomedical Engineering, University of Saskatchewan, Saskatoon SK S7N 5A2, Canada
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Peng Y, Wang Y, Tang N, Sun D, Lan Y, Yu Z, Zhao X, Feng L, Zhang B, Jin L, Yu F, Ma X, Lv C. Andrographolide inhibits breast cancer through suppressing COX-2 expression and angiogenesis via inactivation of p300 signaling and VEGF pathway. J Exp Clin Cancer Res 2018; 37:248. [PMID: 30314513 PMCID: PMC6186120 DOI: 10.1186/s13046-018-0926-9] [Citation(s) in RCA: 116] [Impact Index Per Article: 16.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2018] [Accepted: 10/02/2018] [Indexed: 01/05/2023] Open
Abstract
BACKGROUND Andrographolide (Andro), a diterpenoid lactone, has been used for treatment of various cancers with less adverse effects. However, the underlying mechanisms regarding its anti-tumor mechanism still remain unclear. METHODS Cell viability and proliferation were measured by CCK8 and CFSE dilution assay. The localization of p50/p65 or cytochrome c was determined using confocal immunofluorescence. Streptavidin-agarose pulldown or ChIP assays were used to detect the binding of multiple transactivators to COX-2 promoter. The promoter activity was examined by a dual-Luciferase reporter assay. The functions of Andro on COX-2-mediated angiogenesis were also investigated using human HUVEC cells through tube formation and spheroids sprouting assay. The in vivo anti-tumor efficacy of Andro was analyzed in xenografts nude mice. RESULTS The results indicated that Andro could significantly inhibit the proliferation of human breast cancers, and suppress COX-2 expression at both protein and mRNA levels. Furthermore, Andro could dose-dependently inhibit COX-2-mediated angiogenesis in human endothelial cells. We have also found that Andro significantly promoted the activation of cytochrome c and activated caspase-dependent apoptotic signaling pathway. Our further explorations demonstrated that Andro inhibited the binding of the transactivators CREB2, C-Fos and NF-κB and blocked the recruitment of coactivator p300 to COX-2 promoter. Moreover, Andro could effectively inhibit the activity of p300 histone acetyltransferase (HAT), thereby attenuating the p300-mediated acetylation of NF-κB. Besides, Andro could also dramatically inhibit the migration, invasion and tubulogenesis of HUVECs in vitro. In addition, Andro also exhibited effective anti-tumor efficacy as well as angiogenesis inhibition in vivo. CONCLUSION In current study, we explore the potential effects of Andro in suppressing breast cancer growth and tumor angiogenesis, as well as the precise mechanisms. This work demonstrated the potential anti-cancer effects of Andro, indicating that Andro could inhibit COX-2 expression through attenuating p300 HAT activity and suppress angiogenesis via VEGF pathway, and thereby could be developed as an antitumor agent for the treatment of breast cancer.
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Affiliation(s)
- Yulin Peng
- Institute of Integrative Medicine, College of Pharmacy, College of Basic Medical Science, Dalian Medical University, Dalian, 116044 China
| | - Yan Wang
- Institute of Integrative Medicine, College of Pharmacy, College of Basic Medical Science, Dalian Medical University, Dalian, 116044 China
| | - Ning Tang
- Institute of Integrative Medicine, College of Pharmacy, College of Basic Medical Science, Dalian Medical University, Dalian, 116044 China
- Department of Integrative Medicine, Liaoning University of Traditional Chinese Medicine Xinglin College, Shenyang, 110167 China
| | - Dongdong Sun
- Institute of Integrative Medicine, College of Pharmacy, College of Basic Medical Science, Dalian Medical University, Dalian, 116044 China
| | - Yulong Lan
- Institute of Integrative Medicine, College of Pharmacy, College of Basic Medical Science, Dalian Medical University, Dalian, 116044 China
| | - Zhenlong Yu
- Institute of Integrative Medicine, College of Pharmacy, College of Basic Medical Science, Dalian Medical University, Dalian, 116044 China
- Emergency Department, The Second Affiliated Hospital of Hainan Medical University, Haikou, 571199 China
| | - Xinyu Zhao
- Institute of Integrative Medicine, College of Pharmacy, College of Basic Medical Science, Dalian Medical University, Dalian, 116044 China
| | - Lei Feng
- Institute of Integrative Medicine, College of Pharmacy, College of Basic Medical Science, Dalian Medical University, Dalian, 116044 China
- Emergency Department, The Second Affiliated Hospital of Hainan Medical University, Haikou, 571199 China
| | - Baojing Zhang
- Institute of Integrative Medicine, College of Pharmacy, College of Basic Medical Science, Dalian Medical University, Dalian, 116044 China
| | - Lingling Jin
- Institute of Integrative Medicine, College of Pharmacy, College of Basic Medical Science, Dalian Medical University, Dalian, 116044 China
| | - Fabiao Yu
- Emergency Department, The Second Affiliated Hospital of Hainan Medical University, Haikou, 571199 China
| | - Xiaochi Ma
- Institute of Integrative Medicine, College of Pharmacy, College of Basic Medical Science, Dalian Medical University, Dalian, 116044 China
- Emergency Department, The Second Affiliated Hospital of Hainan Medical University, Haikou, 571199 China
| | - Chuanzhu Lv
- Emergency Department, The Second Affiliated Hospital of Hainan Medical University, Haikou, 571199 China
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Zhu Q, Zheng P, Zhou J, Chen X, Feng Y, Wang W, Zhou F, He Q. Andrographolide affects Th1/Th2/Th17 responses of peripheral blood mononuclear cells from ulcerative colitis patients. Mol Med Rep 2018; 18:622-626. [PMID: 29749556 DOI: 10.3892/mmr.2018.8992] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2017] [Accepted: 04/12/2018] [Indexed: 11/06/2022] Open
Abstract
Ulcerative colitis (UC) is a chronic, idiopathic, inflammatory bowel disease of the colon. T cell responses have been associated with the pathology of UC. Andrographis paniculata (AP) extract has been previously reported as an effective treatment of UC. The present study aimed to explore the effects of andrographolide, the primary active component of AP, on the T cell responses of patients with UC. Peripheral blood mononuclear cells (PBMCs) were isolated from patients with UC and treated with various concentrations of andrographolide (0, 10, 20 and 30 µg/ml). Andrographolide decreased interferon γ, interleukin (IL)‑23 and IL‑17A, however it increased IL‑4 in a dose‑dependent manner, as indicated by ELISA assay. Andrographolide treatment resulted in a decreased percentage of T helper (Th)1 and Th17 cells and an increased proportion of Th2 cells, as demonstrated by flow cytometry analysis. T‑bet (a Th1‑specific transcription factor) and RAR‑related orphan receptor γt (key transcription factor of Th17 cells) expression was decreased, but GATA‑3 (Th2 lineage‑specific transcription factor) expression was increased following andrographolide treatment as indicated by western blot analysis. These results demonstrated the inhibitory effects on Th1/Th17 responses and the promoting effects on Th2 responses of andrographolide. Experiments on IL‑23‑treated PBMCs from healthy donors revealed similar effects of andrographolide on Th1/Th2/Th17 responses. In summary, these results suggest that andrographolide may be an effective candidate for the treatment of IL‑23‑mediated diseases.
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Affiliation(s)
- Qin Zhu
- Department of Gastroenterology, Zhejiang Hospital, Hangzhou, Zhejiang 310013, P.R. China
| | - Peifen Zheng
- Department of Gastroenterology, Zhejiang Hospital, Hangzhou, Zhejiang 310013, P.R. China
| | - Jianying Zhou
- Department of Gastroenterology, Zhejiang Hospital, Hangzhou, Zhejiang 310013, P.R. China
| | - Xinyu Chen
- Department of Gastroenterology, Zhejiang Hospital, Hangzhou, Zhejiang 310013, P.R. China
| | - Yuliang Feng
- Department of Gastroenterology, Zhejiang Hospital, Hangzhou, Zhejiang 310013, P.R. China
| | - Weifeng Wang
- Department of Gastroenterology, Zhejiang Hospital, Hangzhou, Zhejiang 310013, P.R. China
| | - Feng Zhou
- Department of Gastroenterology, Zhejiang Hospital, Hangzhou, Zhejiang 310013, P.R. China
| | - Qiaona He
- Department of Gastroenterology, Zhejiang Hospital, Hangzhou, Zhejiang 310013, P.R. China
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Lucas S, Leach M, Kumar S. Complementary and alternative medicine utilisation for the management of acute respiratory tract infection in children: A systematic review. Complement Ther Med 2018; 37:158-166. [PMID: 29609928 DOI: 10.1016/j.ctim.2018.03.001] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2017] [Revised: 03/02/2018] [Accepted: 03/02/2018] [Indexed: 12/26/2022] Open
Abstract
INTRODUCTION As many as one in two children across the globe use complementary and alternative medicine (CAM) to manage a health condition. Despite the high prevalence of use, there is still limited information on the types of CAM used in children, particularly for the management of one of the most common childhood health complaints - acute respiratory tract infection (ARTI). This systematic review was undertaken to address this knowledge gap. METHODS Eligible studies reporting the use of CAM in children with ARTI were identified using a targeted search of seven electronic databases and the grey literature. Data were extracted using a customised data extraction form and appraised using the McMaster critical review forms for quantitative and qualitative studies. Findings were synthesised in narrative form. RESULTS The search identified 2261 papers, of which 22 studies were eligible for inclusion. The 22 studies reported the use of 118 distinct CAM interventions for the management of ARTI in children. Most (53%, n = 63) of these interventions represented biologically-based therapies, followed by whole medical systems/alternative medical systems (46%, n = 55). No studies reported the use of energy therapies, or manipulative and body-based methods, or mind-body therapies. CONCLUSION A diverse range of CAM interventions are used in the management of ARTI in children. These interventions largely represent CAM use in the southern region of Asia - India, Pakistan and Bangladesh. Further research is needed to better understand the types of CAM used among children with ARTI in western countries.
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Affiliation(s)
- S Lucas
- School of Health Sciences, University of South Australia, Adelaide, South Australia, North Tce. Adelaide SA 5000, Australia.
| | - M Leach
- Department of Rural Health, University of South Australia Adelaide, South Australia, North Tce. Adelaide SA 5000, Australia.
| | - S Kumar
- School of Health Sciences, University of South Australia, Adelaide, South Australia, North Tce. Adelaide SA 5000, Australia.
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Andrographolide enhances cisplatin-mediated anticancer effects in lung cancer cells through blockade of autophagy. Anticancer Drugs 2017; 28:967-976. [PMID: 28692436 DOI: 10.1097/cad.0000000000000537] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Lung cancer is the most common cause of cancer-related death worldwide and the platinum-based drugs such as cisplatin have been used as the first line of the treatment. However, the clinical effectiveness of such chemotherapy is limited by intrinsic or acquired resistance. In this study, we found that cisplatin induced autophagy that attenuated the sensitivity of both A549 and Lewis lung cancer (LLC) cells to cisplatin. In contrast, the clinical drug andrographolide (Andro) suppressed autophagy and enhanced cisplatin-mediated apoptosis in these cells. Using two murine lung cancer models, including a subcutaneously inoculated LLC model and an orthotopic LLC implantation model, we investigated the therapeutic efficacy of the combined treatment of cisplatin and Andro. Compared with the sole cisplatin treatment, combining cisplatin with Andro potentially inhibited tumor growth, reduced the incidence of lung metastases, and relieved renal tubular damage. Moreover, the combined treatment prolonged the life span of tumor-bearing mice. TUNEL and immunohistochemistry assays showed the increase in apoptotic cells and the decrease in both conversion of LC3B-I to LC3B-II and Atg5 protein expression in the tumor tissues from mice with the combined treatment. These results suggest that Andro offers an ideal candidate of autophagy inhibitors in clinical application, and combination of cisplatin with Andro could be a promising strategy for the treatment of lung cancer.
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Tran QT, Wong WF, Chai CL. Labdane diterpenoids as potential anti-inflammatory agents. Pharmacol Res 2017; 124:43-63. [PMID: 28751221 DOI: 10.1016/j.phrs.2017.07.019] [Citation(s) in RCA: 60] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2017] [Revised: 07/21/2017] [Accepted: 07/21/2017] [Indexed: 01/20/2023]
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Guo BJ, Bian ZX, Qiu HC, Wang YT, Wang Y. Biological and clinical implications of herbal medicine and natural products for the treatment of inflammatory bowel disease. Ann N Y Acad Sci 2017; 1401:37-48. [DOI: 10.1111/nyas.13414] [Citation(s) in RCA: 61] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2017] [Revised: 05/15/2017] [Accepted: 05/18/2017] [Indexed: 12/13/2022]
Affiliation(s)
- Bao-Jian Guo
- State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences; University of Macau; Taipa Macao SAR China
| | - Zhao-Xiang Bian
- School of Chinese Medicine and Hong Kong Chinese Medicine Study Centre; Hong Kong Baptist University; Kowloon Tong Hong Kong China
| | - Hong-Cong Qiu
- Guangxi Institute of Traditional Medical and Pharmaceutical Sciences and Guangxi Key Laboratory of Traditional Chinese Medicine Quality Standards; Nanning China
| | - Yi-Tao Wang
- State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences; University of Macau; Taipa Macao SAR China
| | - Ying Wang
- State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences; University of Macau; Taipa Macao SAR China
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Hu XY, Wu RH, Logue M, Blondel C, Lai LYW, Stuart B, Flower A, Fei YT, Moore M, Shepherd J, Liu JP, Lewith G. Andrographis paniculata (Chuān Xīn Lián) for symptomatic relief of acute respiratory tract infections in adults and children: A systematic review and meta-analysis. PLoS One 2017; 12:e0181780. [PMID: 28783743 PMCID: PMC5544222 DOI: 10.1371/journal.pone.0181780] [Citation(s) in RCA: 54] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2016] [Accepted: 07/06/2017] [Indexed: 01/30/2023] Open
Abstract
INTRODUCTION Antimicrobial resistance (AMR) is a substantial threat to public health. Safe and effective alternatives are required to reduce unnecessary antibiotic prescribing. Andrographis Paniculata (A. Paniculata, Chuān Xīn Lián) has traditionally been used in Indian and Chinese herbal medicine for cough, cold and influenza, suggesting a role in respiratory tract infections (RTIs). This systematic review aimed to evaluate the clinical effectiveness and safety of A. Paniculata for symptoms of acute RTIs (ARTIs). MATERIALS AND METHODS English and Chinese databases were searched from their inception to March 2016 for randomised controlled trials (RCTs) evaluating oral A. Paniculata without language barriers (Protocol ID: CRD42016035679). The primary outcomes were improvement in ARTI symptoms and adverse events (AEs). A random effects model was used to pool the mean differences and risk ratio with 95% CI reported. Methodological quality was evaluated using the Cochrane risk of bias tool; two reviewers independently screened eligibility and extracted data. RESULTS Thirty-three RCTs (7175 patients) were included. Most trials evaluated A. Paniculata (as a monotherapy and as a herbal mixture) provided commercially but seldom reported manufacturing or quality control details. A. Paniculata improved cough (n = 596, standardised mean difference SMD: -0.39, 95% confidence interval CI [-0.67, -0.10]) and sore throat (n = 314, SMD: -1.13, 95% CI [-1.37, -0.89]) when compared with placebo. A. Paniculata (alone or plus usual care) has a statistically significant effect in improving overall symptoms of ARTIs when compared to placebo, usual care, and other herbal therapies. Evidence also suggested that A. Paniculata (alone or plus usual care) shortened the duration of cough, sore throat and sick leave/time to resolution when compared versus usual care. No major AEs were reported and minor AEs were mainly gastrointestinal. The methodological quality of included trials was overall poor. CONCLUSIONS A. Paniculata appears beneficial and safe for relieving ARTI symptoms and shortening time to symptom resolution. However, these findings should be interpreted cautiously owing to poor study quality and heterogeneity. Well-designed trials evaluating the effectiveness and potential to reduce antibiotic use of A. Paniculata are warranted.
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Affiliation(s)
- Xiao-Yang Hu
- Primary Care and Population Sciences, Aldermoor Health Centre, Southampton, United Kingdom
| | - Ruo-Han Wu
- Centre for Evidence-Based Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Martin Logue
- Primary Care and Population Sciences, Aldermoor Health Centre, Southampton, United Kingdom
| | - Clara Blondel
- AgroParisTech, Paris Institute of Technology for Life, Food and Environmental Sciences, Paris, France
| | - Lily Yuen Wan Lai
- Primary Care and Population Sciences, Aldermoor Health Centre, Southampton, United Kingdom
| | - Beth Stuart
- Primary Care and Population Sciences, Aldermoor Health Centre, Southampton, United Kingdom
| | - Andrew Flower
- Primary Care and Population Sciences, Aldermoor Health Centre, Southampton, United Kingdom
| | - Yu-Tong Fei
- Centre for Evidence-Based Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Michael Moore
- Primary Care and Population Sciences, Aldermoor Health Centre, Southampton, United Kingdom
| | - Jonathan Shepherd
- Southampton Health Technology Assessments Centre (SHTAC), Faculty of Medicine, University of Southampton, Southampton, United Kingdom
| | - Jian-Ping Liu
- Centre for Evidence-Based Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - George Lewith
- Primary Care and Population Sciences, Aldermoor Health Centre, Southampton, United Kingdom
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Inhibitory effects of andrographolide on activated macrophages and adjuvant-induced arthritis. Inflammopharmacology 2017; 26:447-456. [DOI: 10.1007/s10787-017-0375-7] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2017] [Accepted: 07/12/2017] [Indexed: 12/30/2022]
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Chen S, Hu H, Miao S, Zheng J, Xie Z, Zhao H. Anti-tumor effect of cisplatin in human oral squamous cell carcinoma was enhanced by andrographolide via upregulation of phospho-p53 in vitro and in vivo. Tumour Biol 2017; 39:1010428317705330. [PMID: 28513299 DOI: 10.1177/1010428317705330] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Oral squamous cell carcinoma is one of the most common neoplasm in the world. Despite the improvements in diagnosis and treatment, the outcome is still poor now. Thus, the development of novel therapeuticapproaches is needed. The aim of this study is to assess the synergistic anti-tumor effect of andrographolide with cisplatin (DDP) in oral squamous cell carcinoma CAL-27 cells in vitro and in vivo. We performed Cell Counting Kit-8 proliferation assay, apoptosis assay, and western blotting on CAL-27 cells treated with andrographolide, DDP or the combination in vitro. In vivo, we also treated CAL-27 xenografts with andrographolide or the combination, and performed terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling assay and immunohistochemical analysis of Ki-67. The results showed the combination of andrographolide and DDP synergistically inhibited CAL-27 cell proliferation in vitro and caused tumor regression in vivo in the CAL-27 xenografts. In addition, the synergistic anti-tumor effect of andrographolide with synergistic was due to an enhanced apoptosis. Moreover, the combination therapy upregulated the expression level of p-p53 in vitro and decreased Ki-67 expression in vivo. Our data indicate that the combination treatment of andrographolide and DDP results in synergistic anti-tumor growth activity against oral squamous cell carcinoma CAL-27 in vitro and in vivo. These results demonstrated that combination of andrographolide with DDP was likely to represent a potential therapeutic strategy for oral squamous cell carcinoma.
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Affiliation(s)
- Songjie Chen
- 1 Department of Stomatology, Wenzhou People's Hospital, Wenzhou, China
| | - Hui Hu
- 1 Department of Stomatology, Wenzhou People's Hospital, Wenzhou, China
| | - Shushu Miao
- 1 Department of Stomatology, Wenzhou People's Hospital, Wenzhou, China
| | - Jiayong Zheng
- 1 Department of Stomatology, Wenzhou People's Hospital, Wenzhou, China
| | - Zhijian Xie
- 2 Oral and Maxillofacial Surgery, Affiliated Hospital for Stomatology of Zhejiang University School of Medicine, Hangzhou, China
| | - Hui Zhao
- 1 Department of Stomatology, Wenzhou People's Hospital, Wenzhou, China
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Mi S, Xiang G, Yuwen D, Gao J, Guo W, Wu X, Wu X, Sun Y, Su Y, Shen Y, Xu Q. Inhibition of autophagy by andrographolide resensitizes cisplatin-resistant non-small cell lung carcinoma cells via activation of the Akt/mTOR pathway. Toxicol Appl Pharmacol 2016; 310:78-86. [DOI: 10.1016/j.taap.2016.09.009] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2016] [Revised: 09/12/2016] [Accepted: 09/13/2016] [Indexed: 01/23/2023]
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Oligo-polyethene glycol (PEG)-modified 14-deoxy-11,12-didehydroandrographolide derivatives: synthesis, solubility and anti-bacterial activity. Tetrahedron 2016. [DOI: 10.1016/j.tet.2016.03.025] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
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Banerjee M, Chattopadhyay S, Choudhuri T, Bera R, Kumar S, Chakraborty B, Mukherjee SK. Cytotoxicity and cell cycle arrest induced by andrographolide lead to programmed cell death of MDA-MB-231 breast cancer cell line. J Biomed Sci 2016; 23:40. [PMID: 27084510 PMCID: PMC4833932 DOI: 10.1186/s12929-016-0257-0] [Citation(s) in RCA: 66] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2015] [Accepted: 04/03/2016] [Indexed: 11/10/2022] Open
Abstract
Background Breast cancer is considered as an increasing major life-threatening concern among the malignancies encountered globally in females. Traditional therapy is far from satisfactory due to drug resistance and various side effects, thus a search for complementary/alternative medicines from natural sources with lesser side effects is being emphasized. Andrographis paniculata, an oriental, traditional medicinal herb commonly available in Asian countries, has a long history of treating a variety of diseases, such as respiratory infection, fever, bacterial dysentery, diarrhea, inflammation etc. Extracts of this plant showed a wide spectrum of therapeutic effects, such as anti-bacterial, anti-malarial, anti-viral and anti-carcinogenic properties. Andrographolide, a diterpenoid lactone, is the major active component of this plant. This study reports on andrographolide induced apoptosis and its possible mechanism in highly proliferative, invasive breast cancer cells, MDA-MB-231 lacking a functional p53 and estrogen receptor (ER). Furthermore, the pharmacokinetic properties of andrographolide have also been studied in mice following intravenous and oral administration. Results Andrographolide showed a time- and concentration- dependent inhibitory effect on MDA-MB-231 breast cancer cell proliferation, but the treatment did not affect normal breast epithelial cells, MCF-10A (>80 %). The number of cells in S as well as G2/M phase was increased after 36 h of treatment. Elevated reactive oxygen species (ROS) production with concomitant decrease in Mitochondrial Membrane Potential (MMP) and externalization of phosphatidyl serine were observed. Flow cytometry with Annexin V revealed that the population of apoptotic cells increased with prolonged exposure to andrographolide. Activation of caspase-3 and caspase-9 were also noted. Bax and Apaf-1 expression were notably increased with decreased Bcl-2 and Bcl-xL expression in andrographolide-treated cells. Pharmacokinetic study with andrographolide showed the bioavailability of 9.27 ± 1.69 % with a Cmax, of 0.73 ± 0.17 μmol/L and Tmax of 0.42 ± 0.14 h following oral administration. AG showed rapid clearance and moderate terminal half lives (T1/2) of 1.86 ± 0.21 and 3.30 ± 0.35 h following IV and oral administration respectively. Conclusion This investigation indicates that andrographolide might be useful as a possible chemopreventive/chemotherapeutic agent for human breast cancers. Electronic supplementary material The online version of this article (doi:10.1186/s12929-016-0257-0) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Malabika Banerjee
- Department of Microbiology, University of Kalyani, Kalyani, 741235, WB, India.,TCG Life Science Ltd., Bengal Intelligent Park, Tower-B, Block-EP & GP, Sector-5, Salt Lake, Kolkata, 700091, India
| | - Subrata Chattopadhyay
- TCG Life Science Ltd., Bengal Intelligent Park, Tower-B, Block-EP & GP, Sector-5, Salt Lake, Kolkata, 700091, India
| | | | - Rammohan Bera
- TCG Life Science Ltd., Bengal Intelligent Park, Tower-B, Block-EP & GP, Sector-5, Salt Lake, Kolkata, 700091, India
| | - Sanjay Kumar
- TCG Life Science Ltd., Bengal Intelligent Park, Tower-B, Block-EP & GP, Sector-5, Salt Lake, Kolkata, 700091, India
| | - Biswajit Chakraborty
- TCG Life Science Ltd., Bengal Intelligent Park, Tower-B, Block-EP & GP, Sector-5, Salt Lake, Kolkata, 700091, India
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Target identification of covalently binding drugs by activity-based protein profiling (ABPP). Bioorg Med Chem 2016; 24:3291-303. [PMID: 27085673 DOI: 10.1016/j.bmc.2016.03.050] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2016] [Revised: 03/25/2016] [Accepted: 03/26/2016] [Indexed: 12/12/2022]
Abstract
The characterization of the target proteins of drug molecules has become an important goal in understanding its mode of action and origin of side effects due to off-target binding. This is especially important for covalently binding drugs usually containing electrophilic moieties, which potentially can react with nucleophilic residues found in many proteins. This review gives a comprehensive overview of the use of activity-based protein profiling (ABPP) as an efficient tool for the target identification of covalently binding drugs.
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Barth A, Hovhannisyan A, Jamalyan K, Narimanyan M. Antitussive effect of a fixed combination of Justicia adhatoda, Echinacea purpurea and Eleutherococcus senticosus extracts in patients with acute upper respiratory tract infection: A comparative, randomized, double-blind, placebo-controlled study. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2015; 22:1195-1200. [PMID: 26598919 DOI: 10.1016/j.phymed.2015.10.001] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/20/2015] [Revised: 10/02/2015] [Accepted: 10/04/2015] [Indexed: 06/05/2023]
Abstract
BACKGROUND Kan Jang® oral solution (KJ) is a fixed combination of aqueous ethanolic extracts of Justicia adhatoda L. leaf, Echinacea purpurea (L.) Moench root, and Eleutherococcus senticosus (Rupr. & Maxim.) Harms root. It is approved in Scandinavia as an herbal medicinal product for respiratory tract infection treatment. PURPOSE The present clinical trial aimed to compare the antitussive effect of KJ with placebo (PL) and bromhexine (BH) among patients of 18-65 years old with non-complicated upper respiratory infections (URI; i.e., common cold). STUDY DESIGN We performed a parallel-group, randomized, double-blinded, placebo-controlled trial in in 177 patients with acute URI over a 5 day period. METHODS We investigated the antitussive effects of a KJ (30 ml/day; 762 mg genuine extracts with standardized contents of 0.2 mg/ml vasicine, 0.8 mg/ml chicoric acid, and 0.03 mg/ml eleutherosides B and E), bromhexine hydrochloride (24 mg/30 ml/day) and PL on cough and blood markers. The primary outcome was cough relief, which was assessed as the change of cough frequency from baseline (cough index). Secondary outcomes were safety with regards to reported adverse events (AEs) and hematological data. RESULTS Both KJ and BH relieved cough more effectively than placebo. On the third and fourth days of treatment, we observed faster improvement in the group receiving KJ compared to in the groups receiving BH (100%) or PL (100%), indicating a slightly shorter recovery time in the KJ group. KJ showed a good tolerability and safety profile. CONCLUSION KJ exerted significant antitussive effects in URI. The present data further support the therapeutic use of KJ in upper respiratory tract infections.
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Affiliation(s)
- Anders Barth
- Partus Kvinnohälsa, Södra v. 2, 412 54, Göteborg
| | - Areg Hovhannisyan
- Anti-doping Service of Republican Centre of Sport Medicine, Acharyan Street, 2/6, Yerevan, Armenia .
| | - Kristina Jamalyan
- Yerevan State Medical University of Armenia, Koryun 2 0025, Yerevan, Armenia
| | - Mikael Narimanyan
- Yerevan State Medical University of Armenia, Koryun 2 0025, Yerevan, Armenia
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Yusof NA, Isha A, Ismail IS, Khatib A, Shaari K, Abas F, Rukayadi Y. Infrared-metabolomics approach in detecting changes in Andrographis paniculata metabolites due to different harvesting ages and times. JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE 2015; 95:2533-2543. [PMID: 25371390 DOI: 10.1002/jsfa.6987] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/12/2014] [Revised: 10/31/2014] [Accepted: 10/31/2014] [Indexed: 06/04/2023]
Abstract
BACKGROUND The metabolite changes in three germplasm accessions of Malaysia Andrographis paniculata (Burm. F.) Nees, viz. 11265 (H), 11341 (P) and 11248 (T), due to their different harvesting ages and times were successfully evaluated by attenuated total reflectance (ATR)-Fourier transform infrared (FTIR) spectroscopy and translated through multivariate data analysis of principal component analysis (PCA) and orthogonal partial least square-discriminant analysis (OPLS-DA). This present study revealed the feasibility of ATR-FTIR in detecting the trend changes of the major metabolites - andrographolide and neoandrographolide - functional groups in A. paniculata leaves of different accessions. The harvesting parameter was set at three different ages of 120, 150 and 180 days after transplanting (DAT) and at two different time sessions of morning (7:30-10:30 am) and evening (2:30-5.30 pm). RESULTS OPLS-DA successfully discriminated the A. paniculata crude extracts into groups of which the main constituents - andrographolide and neoandrographolide - could be mainly observed in the morning session of 120 DAT for P and T, while H gave the highest intensities of these constituents at 150 DAT. CONCLUSION The information extracted from ATR-FTIR data through OPLS-DA could be useful in tailoring this plant harvest stage in relation to the content of its two major diterpene lactones: andrographolide and neoandrographolide.
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Affiliation(s)
- Nur A'thifah Yusof
- Laboratory of Natural Products, Institute of Bioscience, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia
| | - Azizul Isha
- Laboratory of Natural Products, Institute of Bioscience, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia
| | - Intan Safinar Ismail
- Laboratory of Natural Products, Institute of Bioscience, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia
| | - Alfi Khatib
- Laboratory of Natural Products, Institute of Bioscience, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia
- Kuliyyah of Pharmacy, International Islamic University Malaysia, 25710 Kuantan, Pahang, Malaysia
| | - Khozirah Shaari
- Laboratory of Natural Products, Institute of Bioscience, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia
| | - Faridah Abas
- Laboratory of Natural Products, Institute of Bioscience, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia
| | - Yaya Rukayadi
- Laboratory of Natural Products, Institute of Bioscience, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia
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Li L, Wijaya H, Samanta S, Lam Y, Yao SQ. In situ imaging and proteome profiling indicate andrographolide is a highly promiscuous compound. Sci Rep 2015; 5:11522. [PMID: 26105662 PMCID: PMC4478469 DOI: 10.1038/srep11522] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2015] [Accepted: 05/28/2015] [Indexed: 01/07/2023] Open
Abstract
Natural products represent an enormous source of pharmacologically useful compounds, and are often used as the starting point in modern drug discovery. Many biologically interesting natural products are however not being pursued as potential drug candidates, partly due to a lack of well-defined mechanism-of-action. Traditional in vitro methods for target identification of natural products based on affinity protein enrichment from crude cellular lysates cannot faithfully recapitulate protein-drug interactions in living cells. Reported herein are dual-purpose probes inspired by the natural product andrographolide, capable of both reaction-based, real-time bioimaging and in situ proteome profiling/target identification in live mammalian cells. Our results confirm that andrographolide is a highly promiscuous compound and engaged in covalent interactions with numerous previously unknown cellular targets in cell type-specific manner. We caution its potential therapeutic effects should be further investigated in detail.
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Affiliation(s)
- Lin Li
- 1] Department of Chemistry, National University of Singapore, Singapore 117543 [2] Key Laboratory of Flexible Electronics (KLOFE) &Institute of Advanced Materials (IAM), National Jiangsu Synergistic Innovation Center for Advanced Materials (SICAM), Nanjing Tech University (NanjingTech), Nanjing 211816, P. R. China
| | - Hadhi Wijaya
- Department of Chemistry, National University of Singapore, Singapore 117543
| | - Sanjay Samanta
- Department of Chemistry, National University of Singapore, Singapore 117543
| | - Yulin Lam
- Department of Chemistry, National University of Singapore, Singapore 117543
| | - Shao Q Yao
- Department of Chemistry, National University of Singapore, Singapore 117543
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Andrographolide radiosensitizes human ovarian cancer SKOV3 xenografts due to an enhanced apoptosis and autophagy. Tumour Biol 2015; 36:8359-65. [DOI: 10.1007/s13277-015-3578-9] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2015] [Accepted: 05/15/2015] [Indexed: 12/11/2022] Open
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Tsai MF, Wang CC, Chen JJW. Tumour suppressor HLJ1: A potential diagnostic, preventive and therapeutic target in non-small cell lung cancer. World J Clin Oncol 2014; 5:865-873. [PMID: 25493224 PMCID: PMC4259948 DOI: 10.5306/wjco.v5.i5.865] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2013] [Revised: 02/10/2014] [Accepted: 04/16/2014] [Indexed: 02/06/2023] Open
Abstract
Lung cancer is the leading cause of cancer-related mortality throughout the world. Non-small cell lung cancer (NSCLC) accounts for 85% of all diagnosed lung cancers. Despite considerable progress in the diagnosis and treatment of the disease, the overall 5-year survival rate of NSCLC patients remains lower than 15%. The most common causes of death in lung cancer patients are treatment failure and metastasis. Therefore, developing novel strategies that target both tumour growth and metastasis is an important and urgent mission for the next generation of anticancer therapy research. Heat shock proteins (HSPs), which are involved in the fundamental defence mechanism for maintaining cellular viability, are markedly activated during environmental or pathogenic stress. HSPs facilitate rapid cell division, metastasis, and the evasion of apoptosis in cancer development. These proteins are essential players in the development of cancer and are prime therapeutic targets. In this review, we focus on the current understanding of the molecular mechanisms responsible for HLJ1’s role in lung cancer carcinogenesis and progression. HLJ1, a member of the human HSP 40 family, has been characterised as a tumour suppressor. Research studies have also reported that HLJ1 shows promising dual anticancer effects, inhibiting both tumour growth and metastasis in NSCLC. The accumulated evidence suggests that HLJ1 is a potential biomarker and treatment target for NSCLC.
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Zhou J, Hu SE, Tan SH, Cao R, Chen Y, Xia D, Zhu X, Yang XF, Ong CN, Shen HM. Andrographolide sensitizes cisplatin-induced apoptosis via suppression of autophagosome-lysosome fusion in human cancer cells. Autophagy 2014; 8:338-49. [DOI: 10.4161/auto.18721] [Citation(s) in RCA: 85] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023] Open
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50
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Andrographolide induces vascular smooth muscle cell apoptosis through a SHP-1-PP2A-p38MAPK-p53 cascade. Sci Rep 2014; 4:5651. [PMID: 25007834 PMCID: PMC4090621 DOI: 10.1038/srep05651] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2013] [Accepted: 06/24/2014] [Indexed: 02/06/2023] Open
Abstract
The abnormal growth of vascular smooth muscle cells (VSMCs) is considered a critical pathogenic process in inflammatory vascular diseases. We have previously demonstrated that protein phosphatase 2 A (PP2A)-mediated NF-κB dephosphorylation contributes to the anti-inflammatory properties of andrographolide, a novel NF-κB inhibitor. In this study, we investigated whether andrographolide causes apoptosis, and characterized its apoptotic mechanisms in rat VSMCs. Andrographolide activated the p38 mitogen-activated protein kinase (p38MAPK), leading to p53 phosphorylation. Phosphorylated p53 subsequently transactivated the expression of Bax, a pro-apoptotic protein. Transfection with pp2a small interfering RNA (siRNA) suppressed andrographolide-induced p38MAPK activation, p53 phosphorylation, and caspase 3 activation. Andrographolide also activated the Src homology 1 domain-containing protein tyrosine phosphatase (SHP-1), and induced PP2A dephosphorylation, both of which were inhibited by the SHP-1 inhibitor sodium stibogluconate (SSG) or shp-1 siRNA. SSG or shp-1 siRNA prevented andrographolide-induced apoptosis. These results suggest that andrographolide activates the PP2A-p38MAPK-p53-Bax cascade, causing mitochondrial dysfunction and VSMC death through an SHP-1-dependent mechanism.
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