Gout is a metabolic disorder accompanied by high serum uric acid levels and joint inflammation due to disturbances in purine metabolism in the body. The dried fruit of Terminalia chebula Retz. is recorded in the "Four Medical Tantras" for the treatment of gout and the core anti-gout component of the Tibetan clinical prescription, such as TongFengTangSan. However, the anti-gout efficacy has not been reported yet.

To evaluate the anti-gout effect and mechanisms of Terminalia chebula Retz. in gout model rats.

First, the components of the Terminalia chebula Retz. extract were detected and characterized using ultra performance liquid chromatography with quadrupole time-of-flight mass spectrometry technology. A gout model was established using the continuous intragastric administration of 200 mg/kg of potassium oxonate and 300 mg/kg of hypoxanthine for 44 days, and 8 mg monosodium urate suspension was injected once in the joint cavity on the 42nd day. One hour after modeling, Terminalia chebula Retz. extract was administered by gavage at low, medium, and high doses. The corresponding biochemical indicators at the protein and gene levels were detected by real-time quantitative polymerase chain reaction (RT-qPCR) and western blot.

A total of 149 compounds, comprising 23 phenolic acids, 104 tannins, 5 flavonoids, 14 terpenoids, and three other compounds, were identified in Terminalia chebula Retz. extract using the ultra performance liquid chromatography with quadrupole time-of-flight mass spectrometry method. The in vivo pharmacodynamics experiments showed that Terminalia chebula Retz. extract significantly reduced the serum uric acid level, the ankle swelling level, and the level of inflammatory factors in the gout rats. Terminalia chebula Retz. extract also decreased the serum xanthine oxidase, alanine aminotransferase, aspartate aminotransferase and diamine oxidase activity of the gout rats. The western blot and PCR experiments showed that treatment with Terminalia chebula Retz. extract down-regulated the mRNA and protein levels of urate transporter 1 and glucose transporter 9 in the kidney tissues. An immunofluorescence experiment revealed that Terminalia chebula Retz. extract strengthened the intestinal barrier by the up-regulation on the protein expression of occludin and zonula occludens-1 in the ileum. In addition, Terminalia chebula Retz. extract was found to alleviate inflammation by inactivating the renal NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome and the synovial membranes of joints. Terminalia chebula Retz. treatment down-regulated the protein or mRNA levels of NLRP3 inflammasome family members, including toll-like receptor 4, toll-like receptor 2, NLRP3, nuclear factor kappa-B, apoptosis-associated speck-like protein containing a CARD and interleukin-1β.

This study demonstrated that Terminalia chebula Retz. extract alleviated gout symptoms through the dual effects of lowering UA and relieving inflammation through inhibiting NLRP3 inflammasome activation.

Zhachong-13 pills (ZC-13), as a traditional prescription of Mongolian medicine, are often used in the clinical practice of Mongolian hospitals for the treatment of stroke and rheumatic arthritis. In this experiment, UHPLC-Q-Exactive Orbitrap MS was used to explore the chemical composition of ZC-13. The results showed that 315 compounds were identified or inferred, including 56 alkaloids, 77 2-(2-phenylethyl)chromones, 61 flavonoids, 31 tannins, 8 coumarins, 16 lignans, 21 terpenoids, 5 amino acids, 19 organic acids, and 21 other components. In addition, the pharmacological activities related to anti-cerebral ischemia of these components were summarized. This result laid a foundation for further study on the pharmacodynamic material basis of ZC-13 and provided a scientific basis for the formulation of ZC-13 quality specifications.

Diabetic retinopathy is the major cause of vision failure in diabetic patients, and the current treatment involves the practice of glucocorticoids or VEGF antagonists that are "off-label". A few small organic molecules against DR were discovered many years ago. Nutraceuticals are naturally available functional foods that endorse different health benefits, including vitamins, antioxidants, minerals, fatty acids, and amino acids that can defer the development of some diseases.

Numerous studies reported that nutraceuticals encourage multiple therapeutic benefits and provide protection against various diseases. In diabetes, nutraceuticals contribute to improving insulin sensitivity, metabolism regulation, and lower hyperglycemia. The major aim of this study is to discover the most active drug from natural or plant sources. In this work, 42 phytochemical constituents from 4 kinds of plants were docked with the C4 target of diabetic retinopathy by an in silico molecular docking study.

According to the binding energy, all the phytoconstituents possessed good to high attraction towards the target, and 6 phytochemicals, such as terchebulin, punicalagin, chebulagic acid, casuarinin, punicalin, and pedunculagin, disclosed superior binding energy towards the target than standard ruboxistaurin via the interactions of conventional hydrogen bonding, pi-alkyl interactions, etc. Molecular dynamic simulation studies further established the stability of the phytoconstituents, and ADMET studies proved the safety profile of these phytoconstituents.

Hence, the current study suggested that the phytochemicals from various herbs inhibit the C4 target of diabetic retinopathy and can be utilized as lead compounds to develop analogs or repurposed for the treatment of DR.

Hyperuricemia (HUA), a common metabolic disorder associated with gout, renal dysfunction, and systemic inflammation, necessitates safer and more comprehensive therapeutic approaches. Traditional Tibetan medicine has a rich history of treating HUA. This study aimed to identify novel anti-hyperuricemic herb derived from traditional Tibetan medicine.

Traditional Tibetan medicine prescriptions for HUA were analyzed using data mining techniques, identifying T. chebula as a high-frequency herb. Its phytochemical composition was characterized by UPLC-QE-Orbitrap-MS. Hyperuricemic rat models were treated with T. chebula to assess its effects on serum uric acid (UA) levels, renal inflammation, intestinal barrier integrity, and gut microbiota composition. Molecular and histological analyses evaluated its impact on key biomarkers.

Through data mining, we identified T. chebula as a promising candidate for HUA treatment. T. chebula demonstrated dose-dependent inhibition of xanthine oxidase (XOD) in vitro and significantly reduced serum UA levels and XOD activity in vivo. It restored gut barrier function by upregulating tight junction proteins (ZO-1, Occludin, Claudin-1) and reduced pro-inflammatory cytokines (IL-6, TNF-α). T. chebula improved renal function, reducing serum creatinine (Cre) and blood urea nitrogen (BUN) levels. Gut microbiota analysis revealed a favorable shift in microbial composition, with reductions in harmful bacteria (eg, Clostridium spp.) and increases in beneficial bacteria (eg, Roseburia). These effects aligned with the modulation of the gut-kidney axis.

This study highlights the multi-target therapeutic potential of T. chebula in HUA management. By regulating the gut-kidney axis, T. chebula alleviates systemic inflammation, enhances intestinal and renal health, and addresses critical aspects of HUA pathology. These findings underscore the value of integrating traditional medicine with modern scientific methodologies to develop innovative treatments.

Ulcerative colitis is a chronic, refractory disease caused by dysregulation of mucosal immune responses to the indigenous bacterial flora as well as genetic and environmental variables. Recently, there has been increasing interest towards the use of herbal medicines for the treatment of ulcerative colitis and the potential benefits could lie in their high patient acceptability, effectiveness, safety, and relatively low cost. It has been reported that Chebulic myrobalan (Terminalia chebula) exhibits anti-oxidant, anti-inflammatory and immunomodulatory properties. The present study was designed to evaluate the protective potential of extract of dried fruit pulp of T. chebula against Dextran sulphate sodium (DSS)-induced ulcerative colitis in male BALB/c mice. Three cycles of DSS (3 % w/v in drinking water), each followed by a seven-day remission phase were used to induce ulcerative colitis in mice. Animals were treated with T. chebula (300 mg/kg and 600 mg/kg) starting from Ist remission period to the end of the study. Different biochemical assays, histological evaluation and molecular analysis were performed to evaluate the protective effects of T. chebula extract in DSS induced colitis. T. chebula modulates the expression of nuclear factor kappa B, adenosine monophosphate kinase, tumour necrosis factor-alpha, sirtuin 1 and interleukin-1β. Furthermore, it also accorded coloprotective effects against DNA damage, apoptosis, inflammation and nitrosative stress. Finally, it was found that the high dose of the T. chebula extract (600 mg/kg) was found to be more effective than a low dose (300 mg/kg) in restoring the ulcerative colitis induced colonic damage.

Butylated Hydroxytoluene (BHT) is found to exert cellular toxicity through induction of oxidative stress although being used as antioxidant in many food products. This study investigates the protective effects of two herbal compounds Boeravinone B (BB) and Chebulinic acid (CA) in combination (B4C3 i.e. BB 4 µg/mL and CA 3 µg/mL). Key findings revealed that BHT exerted toxicity through induction of ROS (234.47 a.u.) and RNS (0.042 µM/mL), but B4C3 has significantly reduced it (115.46 a.u. and 0.018 µM/mL respecctively). BHT exposure raised the activities of antioxidant enzymes such as SOD (70.9%), CAT (7.08 units/mL), GPX (1.21 units/mL), levels of protein carbonyls (3.52 units/mg) and lipid peroxides (418.34%). Whereas treatment with B4C3 decreased the levels of SOD (29.92%), CAT (3.12 units/mL), GPX (0.36 units/mL), protein carbonyls (0.91 units/mg of protein) and lipid peroxides (106.67%) during BHT exposure. It was found that 20.56% cells were apoptotic while 73.83% were autophagic during BHT treatment. However, proposed phytotherapy rescued the cells from apoptotic and autophagic death and supported cell growth which was confirmed by RT-PCR and growth analysis. Collectively, B4C3 offered a significant protection against BHT-induced cellular damage, suggesting its potential as therapeutic agents for oxidative stress-related hepatotoxicity.

Terminalia chebula Retz., known for its dried fruit, namely Chebulae Fructus, is a medicinal plant with a long-standing global reputation, which was initially recognized for its therapeutic properties during the Jin Dynasty. This review consolidates current knowledge on the traditional uses, phytochemistry, pharmacological properties, toxicity, and pharmacokinetics of Chebulae Fructus, highlighting its clinical significance and the promising therapeutic potential of its compounds. To date, studies have identified approximately 149 compounds within the plant, including tannins, phenolic acids, lignans, triterpenes, flavonoids, and volatiles. These compounds confer a broad spectrum of biological activities in vitro and in vivo, such as antioxidant, anti-inflammatory, antiviral, anticancer, antibacterial, hepatoprotective, nephroprotective, neuroprotective, and anti-diabetic, some of which are already integrated into clinical practice. However, despite substantial advancements, considerable gaps remain in understanding the complete mechanisms of action, pharmacokinetics, and safety profiles of its extracts and compounds. This paper advocates for enhanced focus on these areas to fully elucidate the therapeutic capacities and facilitate the clinical application of Chebulae Fructus. This comprehensive analysis not only reinforces the ethnopharmacological significance of Chebulae Fructus but also lays a foundation for future pharmacological explorations.

To study the efficacy of co-administration of Arshogrit (AG) and Jatyadi Ghrit (JG), two herb-based Ayurvedic medicines, in rat model of croton oil-induced hemorrhoids.

Hemorrhoids refer to a pathological condition affecting the recto-anal region causing pain, swelling, bleeding and protrusion. The available therapies for hemorrhoids are symptomatic or invasive but are expensive and associated with adverse effects. Hence, there exists a need for efficacious and safer pharmacotherapies.

Ultra high performance liquid chromatography detected nine phytocompounds in AG and seven in JG. Seven fatty acids were additionally identified in JG by Gas Chromatography-Mass Spectrometry analysis. The in-vivo efficacy of the co-administration of AG, which was administered orally at the doses of 20, 60 and 200 mg/kg/day and JG, which was topically applied (100 mg/animal/day) was evaluated in Wistar rats by inducing hemorrhoids development with the application of croton oil preparation (COP) in the recto-anal area. Prednisolone was employed as the standard drug and was administered orally at the dose of 1 mg/kg/day.

AG and JG were able to attenuate the croton oil-induced macro and microscopic anomalies. Gross pathological observation demonstrated remarkable decrease in croton oil-induced swelling, hemorrhage and formation of pseudomembrane, with the escalating doses of AG. Microscopic observation revealed alleviation in the histopathological lesions (necrosis, inflammation, hemorrhage/congestion, degeneration and dilatation of blood vessels). AG and JG additionally reduced COP-induced increase in the serum levels of pro-inflammatory cytokines.

This study convincingly demonstrates that co-administration of AG and JG is a potential therapy against hemorrhoids, warranting further investigations.

Terminalia chebula Retz. (T. Chebula, ཨ་རུ་ར།) is highly utilized in ethnic medicine. Its medicinal value is gradually being recognized and shows great potential in the improvement of mild cognitive impairment (MCI) disorders. Tibetan medicine theory classifies this type of disease as one of the "Jie Xie Syndrome (བརྗེད་བྱེད།)." The role of T. Chebula in such diseases has been increasingly studied. This work aimed to elucidate the research progress of T. Chebula in alleviating MCI. The review offers a critical update on the current understanding of the effect of T. Chebula on MCI and highlights new opportunities for exploring its therapeutic potential. This review discusses the role of T. Chebula in alleviating MCI and provides a comprehensive overview of the traditional medicinal uses, chemical composition, toxicology, and quality control aspects of T. Chebula. This review covers 171 chemical constituents and 11 active constituents targeting MCI, such as flavonoids, which can alleviate MCI, primarily through its antioxidative, anti-inflammatory, and neuroprotective properties. T. Chebula shows potential as a natural medicine for the treatment and prevention of MCI. As an important part of ethnomedicinal resources, this work offers valuable insights for future research on T. Chebula-containing ethnomedicines. Research on traditional drug treatments, optimized treatment standards, improved societal knowledge about MCI, and development of an early detection system is essential to the diagnosis and treatment of MCI. These efforts will provide better treatment resources for patients with MCI.

Melasma is a multifactorial, chronic, acquired skin disorder of hyperpigmentation. Terminalia chebula Retz. (T. chebula) has shown antioxidant, anti-inflammatory and tyrosinase enzyme inhibitory activities. So, the present study was designed to evaluate the efficacy of T. chebula 5% cream compared to hydroquinone 2% cream in treating patients with melasma.

The formulation of T. chebula 5% cream was prepared. The stability and release study of the cream were performed. In this randomized, controlled, triple-blind clinical trial, participants with facial melasma were randomly assigned to receive T. chebula 5% cream or hydroquinone 2% cream at bedtime for 12 weeks. Modified Melasma Area and Severity Index (mMASI) scores were recorded for all the participants at the baseline and 4, 8, and 12 weeks after initiating the study.

No statistically significant differences regarding mMASI scores were detected between T. chebula and hydroquinone groups at each time point. The reduction in mMASI scores was statistically significant (p<0.05) in T. chebula group 4, 8, and 12 weeks after initiating the study. However, it reached statistical significance (p<0.05) in hydroquinone group 8, and 12 weeks after the study initiation. The frequencies of side effects especially skin irritation were significantly (p<0.05) lower in T. chebula group.

T. chebula 5% cream could be as effective as hydroquinone 2% cream in treating melasma with fewer side effects.

Type 2 diabetes (T2D) is a metabolic disease of impaired glucose utilization and a major cause of cardiovascular disease (CVD). The pathogenesis of both diseases shares common risk factors and mechanisms, and both are significant contributors to global morbidity and mortality. Supplements of natural products for T2D mellitus (T2DM) and CVD can be seen as a potential preventive and effective therapeutic strategy.

To critically evaluate the therapeutic potential of natural products in T2D and coronary artery disease (CAD).

By using specific keywords, we strategically searched the PubMed database. Randomized controlled trials (RCTs) were searched as the primary focus that examined the effect of natural products on glycemic control, oxidative stress, and antioxidant levels. We focused on outcomes such as low blood glucose levels, adjustment on markers of oxidative stress and antioxidants. After screening full-length papers, we included 9 RCTs in our review that met our inclusion criteria.

In the literature search on the database, we found that various natural products like plant secondary metabolites play a diverse role in the management of CAD. American ginseng, sesame oil and cocoa flavanols proved effective in lowering blood glucose levels and controlling blood pressure, which are key factors in managing T2DM and CVD. In diabetic patients Melissa officinalis effectively reduce inflammation and shows diabetes prevention. Both fish oil and flaxseed oil reduced insulin levels and inflammatory markers, suggesting benefits for both conditions. The lipid profile and endothelial function were enhanced by Nigella sativa oil and Terminalia chebula, which is significant for the management of cardiovascular risk factors in T2DM. Additionally Bilberry extract also showed promise for improving glycemic control in patients with T2DM.

The high level of antioxidant, anti-inflammatory, and anti-angiogenic properties found in natural products makes them promising therapeutic options for the management of CAD, with the potential benefit of lowering the risk of CAD.

Rheumatoid Arthritis is an autoimmune disorder that leads to persistent symmetrical polyarthritis accompanied by systemic manifestations. It may lead to an array of deformities and even complications like rheumatoid nodules, carpal tunnel syndrome, adhesive capsulitis, cardiovascular diseases, and many more.

This case report intends to discuss the ayurvedic management of Rheumatoid Arthritis which was complicated by Adhesive Capsulitis.

A 73-year-old male patient was diagnosed with Rheumatoid Arthritis. He had previously undergone allopathic treatment for a year. In June 2023, the patient sought ayurvedic treatment for his ailment and later acquired signs and symptoms of Adhesive Capsulitis. He was given ayurvedic oral medications along with external therapeutic procedures.

There was a significant reduction in the values of the Routine Assessment of Patient Index Data 3 (RAPID3) score, Clinical Disease Activity Index (CDAI), Rheumatoid Factor (Quantitative), Visual Analogue Scale (VAS), and improvement in the range of movement of the affected joint.

Ayurvedic medicines are effective in managing Rheumatoid Arthritis along with the complication of Adhesive Capsulitis.

Changan powder (CAP) is mainly used to treat various intestinal diseases. Few studies on CAP have been reported; therefore, it is necessary to clarify the material basis of CAP to lay the foundation for further elucidating its functional mechanism and support the rational use of drugs.

In the present study, we aimed to propose a methodology for the quality control of CAP based on qualitative and quantitative analysis of its components.

An ultra-performance liquid chromatography coupled with Fourier transform ion cyclotron resonance mass spectrometry (UPLC-FT-ICR-MS) method was developed to identify chemical components in CAP. In addition, fingerprints of 10 different batches of CAP were established, and quantitative analysis based on UPLC was performed to analyze the quality of CAP.

A total of 58 compounds were preliminarily characterized. The similarity of 10 batches of CAP was greater than 0.995, and 23 common peaks were calibrated. Investigation of the quantitative analytical methodology showed that the four components had good linear relationships within their respective concentration ranges (r2 ≥ 0.9992), and the relative standard deviation (RSD) of precision and stability was less than 2%. The RSD of sample recovery ranged from 0.78% to 1.52%.

The established method can quickly and effectively identify the chemical components of CAP and accurately quantify the known components in CAP. The established fingerprinting and content determination method is stable, reliable, and easy to operate and can be applied in quality control and in vivo research on CAP.

Introduction: Hepatocellular carcinoma (HCC) has been a highly common and pathological disease worldwide, while current therapeutic regimens have limitations. Chebulae Fructus, a common herbal medicine in Asia, has been documented to exert potential therapeutic effects on HCC in ancient medicine clinical practice. However, the molecular mechanism underlying its inhibitory effects on HCC requires further investigation. Methods: In this study, the anti-HCC effect of the aqueous extract of Chebulae Fructus (CFE) on human HCC and its underlying mechanism were evaluated. Assays including CCK8, EdU staining, crystal violet staining, cell clone formation, flow cytometry, wound healing, and transwell were used in vitro. The cell-derived xenograft (CDX) and patient-derived xenograft (PDX) models were used in vivo. Transcriptomics analysis, qRT-PCR, ELISA, IHC staining, and Western blotting were employed to determine the mechanism of action of CFE. Results: The results demonstrate that CFE effectively suppressed the proliferation and activity of HepG2 and PLC/PRF/5 HCC cells. CFE also induced apoptosis, and suppressed the migration and invasion abilities of these cells. Furthermore, CFE exhibited inhibitory effects on tumor growth in both H22 and PLC/PRF/5 mouse models, as well as in an HCC PDX model which is derived from patient tumor samples. Moreover, it was identified that CFE treatment specifically suppressed the Apelin/APJ system in HCC cells and tumor tissues. To investigate the role of the Apelin/APJ system in mediating the effects of CFE treatment, an APJ overexpressed cell model is established. Interestingly, it was found that the overexpression of APJ significantly diminished the inhibitory effects of CFE on HCC in vitro. Discussion: Collectively, this study provides compelling evidence that CFE exerts significant anti-HCC effects in cell and animal models. Moreover, our findings suggest that the Apelin/APJ system may play a vital role in the therapeutic effects of CFE against HCC.

Chebulae Fructus (CF) is known as one of the richest sources of hydrolyzable tannins (HTs). In this study, ultra-performance liquid chromatography coupled with a photodiode array detector method was established for simultaneous determination of the 12 common phenolcarboxylic and tannic constituents (PTCs). Using this method, quantitative analysis was accomplished in CF and other four adulterants, including Terminaliae Belliricae Fructus, Phyllanthi Fructus, Chebulae Fructus Immaturus, and Canarii Fructus. Based on a quantitative analysis of the focused compounds, discrimination of CF and other four adulterants was successfully accomplished by hierarchical cluster analysis and principal component analysis. Additionally, the total contents of the 12 compounds that we focused on in this study were unveiled as 148.86 mg/g, 96.14 mg/g, and 18.64 mg/g in exocarp, mesocarp, and endocarp and seed of CF, respectively, and PTCs were witnessed to be the most abundant in the exocarp of CF. Noticeably, the HTs (chebulagic acid, chebulanin acid, chebulinic acid, and punicalagin) were observed to be ultimately degraded to chebulic acid, gallic acid, and ellagic acid during sunlight-drying of the fresh fruits. As a result, our study indicated that CF and its adulterants could be distinguished by the observed 12 PTCs, which were mainly distributed in the exocarp of the fruits. The HTs were prone to degrade into the three simple phenolcarboxylic acids during drying or processing, allowing us to obtain a more comprehensive understanding of the PTCs, with great significance in the improved quality of CF and related products.

Hyperuricemic nephropathy (HN) is a renal injury caused by hyperuricemia and is the main cause of chronic kidney disease and end-stage renal disease. ShiWeiHeZiSan, which is composed mainly of components of Terminalia chebula Retz. And is recorded in the Four Medical Tantras, is a typical traditional Tibetan medicinal formula for renal diseases. Although T. chebula has been reported to improve renal dysfunction and reduce renal cell apoptosis, the specific mechanism of the nephroprotective effects of T. chebula on HN is still unclear.

This study was conducted to evaluate the effects and specific mechanism of T. chebula extract on HN through network pharmacology and in vivo and in vitro experiments.

Potassium oxalate (1.5 g/kg) and adenine (50 mg/kg) were combined for oral administration to establish the HN rat model, and the effects of T. chebula extract on rats in the HN model were evaluated by renal function indices and histopathological examinations. UPLC-Q-Exactive Orbitrap/MS analysis was also conducted to investigate the chemical components of T. chebula extract, and the potential therapeutic targets of T. chebula in HN were predicted by network pharmacology analysis. Moreover, the activation of potential pathways and the expression of related mRNAs and proteins were further observed in HN model rats and uric acid-treated HK-2 cells.

T. chebula treatment significantly decreased the serum uric acid (SUA), blood urea nitrogen (BUN) and serum creatinine (SCr) levels in HN rats and ameliorated renal pathological injury and fibrosis. A total of 25 chemical components in T. chebula extract were identified by UPLC-Q-Exactive Orbitrap/MS analysis, and network pharmacology analysis indicated that the NF-κB pathway was the potential pathway associated with the therapeutic effects of T. chebula extract on HN. RT‒PCR analysis, immunofluorescence staining and ELISA demonstrated that the mRNA and protein levels of TLR4 and MyD88 were significantly decreased in the renal tissue of HN rats after treatment with T. chebula extract at different concentrations, while the phosphorylation of P65 and the secretion of TNF-α and IL-6 were significantly inhibited. The results of in vitro experiments showed that T. chebula extract significantly decreased the protein levels of TLR4, MyD88, p-IκBα and p-P65 in uric acid-treated HK-2 cells and inhibited the nuclear translocation of p65 in these cells. In addition, the expression of inflammatory factors (IL-1β, IL-6 and TNF-α) and fibrotic genes (α-SMA and fibronectin) was significantly downregulated by T. chebula extract treatment, while E-cadherin expression was significantly upregulated.

T. chebula extract exerts nephroprotective effects on HN, such as anti-inflammatory effects and fibrosis improvement, by regulating the TLR4/MyD88/NF-κB axis, which supports the general use of T. chebula in the management of HN and other chronic kidney diseases.

Otitis externa is an inflammatory and infectious disease that affects the external auditory canal. The term otorrhea refers to the outflow of discharge from the ear which is one of the main symptoms of otitis externa along with inflammation. External ear canal pathology or middle ear illness with tympanic membrane perforation is the etiological factor of otorrhea. Otorrhea is an indication of infection. Antimicrobial agents are the conventional treatment of various bacterial and fungal infections, but they have impediments such as resistance development, side effects, patient affordability, etc. The Gandhak Rasayana formulation mentioned in the Ayurvedic text can be a good option for the treatment of various infectious diseases. Karnasrava is a type of ear disease referred to as Vata predominant Tridoshaja disease and it is curable. The term Karnasrava signifies discharge from ear and is self-explanatory. Karnasrava consists of a wide spectrum of diseases and can have a near correlation with otitis externa as per signs and symptoms. Gandhak Rasayana exhibited significant antibacterial, antifungal and anti-inflammatory activity in otitis externa. Evaluating its antibacterial and antifungal activity can provide scientific evidence for the study through the present case report. A 31-year-old male patient registered in OPD at Sane Guruji Hospital, Hadapsar, Pune was clinically diagnosed as Karnasrava (Otitis externa) and pus culture positive for Klebsiella species. We started the treatment with Gandhak Rasayana-an Ayurvedic formulation of 250mg two tablets in the morning and evening with lukewarm water for 21 days. The outcome of the treatment was observed as a reduction in Karnashula (otalgia), Karnasrava (ear discharge), Karnakandu (itching), ear blockage and inflammatory changes. Post-treatment culture was negative for the organism. The improvement was noted in Brighton grading scale from grade III to grade I. Gandhak Rasayana showed significant antibacterial activity in the present case. Evaluating its antibacterial, antifungal and anti-inflammatory activity can provide scientific evidence for the study.

Terminalia chebula Retz., known as the King of Traditional Tibetan Medicine, is widely used for treating various ailments, particularly stomach disorders. It exhibited inhibitory activity against helicobacter pylori.

The exact mechanism by which T. chebula combats H. pylori infection remains unclear. Therefore, this study aimed to investigate its mechanism of action and the key pathways and targets involved.

Minimum inhibitory concentration (MIC) assay, scanning electron microscope, and inhibiting kinetics curves were conducted. The mRNA expressions were measured by RNA-seq analysis and RT-QPCR. ELISA and Western blot were used to detect the changes in proteins. The main compounds were analyzed by High-performance Liquid Chromatography. The interaction between the compound and target was predicted by Molecular Docking.

The study revealed that T. chebula disrupted the structure of H. pylori bacteria and inhibited Cag A protein expression. Additionally, T. chebula can reduce the expression of flaA, flaB, babA, alpA, alpB, ureE, and ureF genes. Furthermore, T. chebula demonstrated its effectiveness in inhibiting the H. pylori-induced inflammatory response by regulating the inflammasome signaling and ER-stress pathway. Moreover, the study discovered that chebulagic acid has anti-HP activity and inhibits the expression of Cag A protein.

T. chebula acts as a natural remedy for combating H. pylori infection. Its ability to disrupt the bacterial structure, inhibit key proteins, regulate inflammatory pathways, and the presence of chebulagic acid contribute to its anti-H. pylori activity.

The mild-natured and bitter-flavored traditional Chinese medicines (MB-TCMs) are an important class of TCMs that have been widely used in clinical practice and recognized as safe long-term treatments for chronic diseases. However, as an important class of TCMs, the panorama of pharmacological effects and the mechanisms of MB-TCMs have not been systemically reviewed. Compelling studies have shown that gut microbiota can mediate the therapeutic activity of TCMs and help to elucidate the core principles of TCM medicinal theory. In this systematic review, we found that MB-TCMs commonly participated in the modulation of metabolic syndrome, intestinal inflammation, nervous system disease and cardiovascular system disease in association with promoting the growth of beneficial bacteria Bacteroides, Akkermansia, Lactobacillus, Bifidobacterium, Roseburia as well as inhibiting the proliferation of harmful bacteria Helicobacter, Enterococcus, Desulfovibrio and Escherichia-Shigella. These alterations, correspondingly, enhance the generation of protective metabolites, mainly including short-chain fatty acids (SCFAs), bile acid (BAs), 5-hydroxytryptamine (5-HT), indole and gamma-aminobutyric acid (GABA), and inhibit the generation of harmful metabolites, such as proinflammatory factors trimethylamine oxide (TAMO) and lipopolysaccharide (LPS), to further exert multiplicative effects for the maintenance of human health through several different signaling pathways. Altogether, this present review has attempted to comprehensively summarize the relationship between MB-TCMs and gut microbiota by establishing the TCMs-gut microbiota-metabolite-signaling pathway-diseases axis, which may provide new insight into the study of TCM medicinal theories and their clinical applications.

Terminalia chebula (T. chebula) comprising chebulinic acid as its principle active constituent is used to cure various diseases. T. chebula and chebulinic acid are used as antimicrobial, antioxidant, antidiabetic, anti-inflammatory, hepatoprotective, antimutagenic, radioprotective, cardioprotective, antiproliferative, antiarthritic, anticaries, and so on.

The objective of this current study is to give an overview of the recent literature and patents of T. chebula and chebulinic acid including methods of its isolation/extraction and their application in the prevention of various cancers and other diseases.

Present research and patents highlighting the anti-cancer potential of T. chebula and chebulinic acid have been studied and discussed keeping in view the scientific novelty and impact.

Both T. chebula and chebulinic acid are currently being explored for their anticancer potential in vitro and in vivo. They are either incorporated alone or in combination with other plants or drugs to show their activity and many clinical trials are also going on various potentials of the plant and chebulinic acid. Novel extraction techniques are also explored and patented. Efforts are being made to improve the bioavailability by developing Novel herbal drug delivery systems of the plant extract or chebulinic acid itself.

Anti-cancer potential of T. chebula and chebulinic acid may be well established by promising clinical trials and may open new interventions in various tumors. Clinical trials in conjunction with standard therapies are required to explore and validate the actual potential of T. chebula and chebulinic acid respectively.

An integrative strategy of UHPLC/IM-QTOF-MS analysis, MS/MS molecular networking (MN), in-house library search, and a collision cross-section (CCS) simulation and comparison was developed for the rapid characterization of the chemical constituents in Chebulae Fructus (CF). A total of 122 Constituents were identified, and most were phenolcarboxylic and tannic compounds. Subsequently, 1,3,6-tri-O-galloyl-β-d-glucose, terflavin A, 1,2,6-tri-O-galloyl-β-d-glucose, punicalagin B, chebulinic acid, chebulagic acid, 1,2,3,4,6-penta-O-galloyl-β-d-glucose, and chebulic acid, among the 23 common constituents of CF, were screened out by UPLC-PDA fingerprinting and multivariate statistical analyses (HCA, PCA, and OPLS-DA). Then, Pearson's correlation analysis and a grey relational analysis were performed for the spectrum-effect correlation between the UPLC fingerprints and the antioxidant capacity of CF, which was finally validated by an UPLC-DPPH• analysis for the main antioxidant constituents. Our study provides a global identification of CF constituents and contributes to the quality control and development of functional foods and preparations dedicated to CF.

Acetylcholinesterase (AChE) is an important therapeutic target for the treatment of Alzheimer's disease (AD), and the development of natural AChE inhibitors as candidates has played a significant role in drug discovery. In this study, the inhibition mechanisms of four ellagitannins, punicalagin, chebulinic acid, geraniin and corilagin, from Terminalia chebula fruits on AChE were investigated systematically by a combination of inhibition kinetics, multi-spectroscopic methods and molecular docking. The kinetic results showed that punicalagin, chebulinic acid and geraniin exhibited strong reversible inhibitory effects on AChE in an uncompetitive manner with the IC50 values of 0.43, 0.50, and 0.51 mM, respectively, while corilagin inhibited AChE activity in a mixed type with the IC50 value of 0.72 mM. The results of fluorescence and UV-vis spectra and fluorescence resonance energy transfer (FRET) revealed that four ellagitannins could significantly quenched the intrinsic fluorescence of AChE though a static quenching along with non-radiative energy transfer. Thermodynamic analyses showed that values of ΔG, ΔH and ΔS were negative, indicating that all binding processes were spontaneous, and the hydrogen bonding and Van der Waals forces might make a great contribution to the formation of inhibitor-AChE complexes. The synchronous fluorescence, three-dimensional (3D) fluorescence, UV-vis, and FT-IR spectra studies suggested that four ellagitannins could lead to alterations in the micro-environment and secondary structure of AChE, and thus the conformational change of AChE. Moreover, molecular docking demonstrated that four ellagitannins could interacted with main amino acid residues of AChE with affinity energies ranging from -9.9 to -8.7 kJ/mol, and further confirmed the above experimental results. This study provided valuable findings for the potential application of four ellagitannins as promising candidates in the exploration of natural AChE inhibitors for the treatment of AD.

Ocular cancers represent a rare pathology. The American Cancer Society estimates that 3,360 cases of ocular cancer occur annually in the United States. The major types of cancers of the eye include ocular melanoma (also known as uveal melanoma), ocular lymphoma, retinoblastoma, and squamous cell carcinoma. While uveal melanoma is one of the primary intraocular cancers with the highest occurrence in adults, retinoblastoma remains the most common primary intraocular cancer in children, and squamous cell carcinoma presents as the most common conjunctival cancer. The pathophysiology of these diseases involves specific cell signaling pathways. Oncogene mutations, tumor suppressor mutations, chromosome deletions/translocations and altered proteins are all described as causal events in developing ocular cancer. Without proper identification and treatment of these cancers, vision loss, cancer spread, and even death can occur. The current treatments for these cancers involve enucleation, radiation, excision, laser treatment, cryotherapy, immunotherapy, and chemotherapy. These treatments present a significant burden to the patient that includes a possible loss of vision and a myriad of side effects. Therefore, alternatives to traditional therapy are urgently needed. Intercepting the signaling pathways for these cancers with the use of naturally occurring phytochemicals could be a way to relieve both cancer burden and perhaps even prevent cancer occurrence. This research aims to present a comprehensive review of the signaling pathways involved in various ocular cancers, discuss current therapeutic options, and examine the potential of bioactive phytocompounds in the prevention and targeted treatment of ocular neoplasms. The current limitations, challenges, pitfalls, and future research directions are also discussed.

In the current research, an aqueous extract of Terminalia chebula fruit was used to produce silver nanoparticles (Ag NPs) in a sustainable manner. UV-visible spectrophotometry, transmission electron microscopy (TEM), and scanning electron microscopy (SEM) were used to characterize the synthesized nanoparticles. Synthesized Ag NPs were detected since their greatest absorption peak was seen at 460 nm. The synthesized Ag NPs were spherical and had an average size of about 50 nm, with agglomerated structures, as shown via SEM and TEM analyses. The biological activities of the synthesized Ag NPs were evaluated in terms of their antibacterial and antioxidant properties, as well as protein leakage and time-kill kinetics assays. The results suggest that the green synthesized Ag NPs possess significant antibacterial and antioxidant activities, making them a promising candidate for therapeutic applications. Furthermore, the study also evaluated the potential toxicological effects of the Ag NPs using zebrafish embryos as a model organism. The findings indicate that the synthesized Ag NPs did not induce any significant toxic effects on zebrafish embryos, further supporting their potential as therapeutic agents. In conclusion, the environmentally friendly production of Ag NPs using the extract from T. chebula is a promising strategy for discovering novel therapeutic agents with prospective uses in biomedicine.

Data available in the literature on the use of herbal products to treat inflammation-related vascular diseases were considered in this study, while also assessing the influence of gender. To this end, the articles published in PubMed over the past 10 years that described the use of plant extracts in randomized clinical trials studying the effectiveness in vascular pathologies were analyzed. The difference in efficacy of plant-derived preparations in female and male subjects was always considered when reporting. The safety profiles of the selected plants were described, reporting unwanted effects in humans and also by searching the WHO database (VigiBase^®). The medicinal plants considered were Allium sativum, Campomanesia xanthocarpa, Sechium edule, Terminalia chebula. Additionally, an innovative type of preparation consisting of plant-derived nanovesicles was also reported.

Background: The fruit of Terminalia chebula has been widely used for a thousand years for treating diarrhea, ulcers, and arthritic diseases in Asian countries. However, the active components of this Traditional Chinese medicine and their mechanisms remain unclear, necessitating further investigation. Objectives: To perform simultaneous quantitative analysis of five polyphenols in T. chebula and evaluate their anti-arthritic effects including antioxidant and anti-inflammatory activity in vitro. Materials and methods: Water, 50% water-ethanol, and pure ethanol were used as extract solvents. Quantitative analysis of gallic acid, corilagin, chebulanin, chebulagic acid, and ellagic acid in the three extracts was performed using high-performance liquid chromatography (HPLC). Antioxidant activity was assessed by the 2,2-diphenylpicrylhydrazyl (DPPH) radical-scavenging assay, and anti-inflammatory activity was evaluated by detecting interleukin (IL)-6 and IL-8 expression in IL-1β-stimulated MH7A cells. Results: The 50% water-ethanol solvent was the optimal solvent yielding the highest total polyphenol content, and the concentrations of chebulanin and chebulagic acid were much higher than those of gallic acid, corilagin, and ellagic acid in the extracts. The DPPH radical-scavenging assay showed that gallic acid and ellagic acid were the strongest antioxidative components, while the other three components showed comparable antioxidative activity. As for the anti-inflammatory effect, chebulanin and chebulagic acid significantly inhibited IL-6 and IL-8 expression at all three concentrations; corilagin and ellagic acid significantly inhibited IL-6 and IL-8 expression at high concentration; and gallic acid could not inhibit IL-8 expression and showed weak inhibition of IL-6 expression in IL-1β-stimulated MH7A cells. Principal component analysis indicated that chebulanin and chebulagic acid were the main components responsible for the anti-arthritic effects of T. chebula. Conclusion: Our findings highlight the potential anti-arthritic role of chebulanin and chebulagic acid from T. chebula.