Flavonoids are naturally occurring compounds found in fruits, vegetables, and other plant-based foods, and they are known for their health benefits, such as UV protection, antioxidant, anti-inflammatory, and antiproliferative properties. This study investigates whether flavonoids, such as quercetin and 2,3-dehydrosilybin, can act as photoactivatable carbon monoxide (CO)-releasing molecules under physiological conditions. CO has been recently recognized as an important signaling molecule. Here, we show that upon direct irradiation, CO was released from both flavonoids in PBS with chemical yields of up to 0.23 equiv, which increased to almost unity by sensitized photooxygenation involving singlet oxygen. Photoreleased CO reduced cellular toxicity caused by high flavonol concentrations, partially restored mitochondrial respiration, reduced superoxide production induced by rotenone and high flavonol levels, and influenced the G0/G1 and G2/M phases of the cell cycle, showing antiproliferative effects. The findings highlight the potential of quercetin and 2,3-dehydrosilybin as CO-photoreleasing molecules with chemopreventive and therapeutic implications in human pathology and suggest their possible roles in plant biology.

There is still no certain effective treatment for vitiligo as a common chronic skin disorder characterized by depigmented patches and loss of skin melanocytes.

This study evaluates the efficacy of oral silymarin combined with hair follicle transplantation compared to follicle transplantation alone in the treatment of refractory vitiligo.

Twenty refractory vitiligo patients were enrolled in this randomized controlled clinical trial, following up for 3 months. One group underwent hair transplantation plus oral silymarin, while the other group underwent follicle transplantation alone. We assessed the progress with Vitiligo Extent Tensity Index (VETI) in both groups and the peri-follicular pigmentation diameter was estimated monthly. The Friedman test for comparing two groups at the end and the Mann-Whitney test for comparing two groups during each month was used.

The mean age was 30.22 (18-59) years, with the male to female ratio of 1:1. The decrease in the VETI and increase in the perifollicular pigmentation was statistically significant between silymarin and another group in monthly follow-up (p-value: 0.019, 0.019, and 0.035, respectively). Finally, the re-pigmentation was notable in silymarin group (p-value <0.001 vs. 0.029, respectively). In addition, both genders had a significant increase in peri-follicular re-pigmentation in the last follow-up (p-value: 0.012 and 0.044, respectively); although the improvement was not statistically significant between genders in each month.

According to our study, silymarin in combination with hair transplantation could be a potential medical treatment for vitiligo; however, further trials are needed to establish the efficacy of combination therapies.

Obesity is associated with a low-grade chronic inflammatory process characterized by higher circulating TNFα levels, thus contributing to insulin resistance. This study evaluated the effect of silybin, the main bioactive component of silymarin, which has anti-inflammatory properties, on TNFα levels and its impact on glucose uptake in the adipocyte cell line 3T3-L1 challenged with two different inflammatory stimuli, TNFα or lipopolysaccharide (LPS). Silybin's pre-treatment effect was evaluated in adipocytes pre-incubated with silybin (30 or 80 µM) before challenging with the inflammatory stimuli (TNFα or LPS). For the post-treatment effect, the adipocytes were first challenged with the inflammatory stimuli and then post-treated with silybin. After treatments, TNFα production, glucose uptake, and GLUT4 protein expression were determined. Both inflammatory stimuli increased TNFα secretion, diminished GLUT4 expression, and significantly decreased glucose uptake. Silybin 30 µM only reduced TNFα secretion after the LPS challenge. Silybin 80 µM as post-treatment or pre-treatment decreased TNFα levels, improving glucose uptake. However, glucose uptake enhancement induced by silybin did not depend on GLUT4 protein expression. These results show that silybin importantly reduced TNFα levels and upregulates glucose uptake, independently of GLUT4 protein expression.

Silibinin, a bioactive component found in milk thistle extract (Silybum marianum), is known to have significant therapeutic potential in the treatment of various liver diseases. It is considered a key element of silymarin, which is traditionally used to support liver function. The main mechanisms of action of silibinin are attributed to its antioxidant properties protecting liver cells from damage caused by free radicals. Experimental studies conducted in vitro and in vivo have confirmed its ability to inhibit inflammatory and fibrotic processes, as well as promote the regeneration of damaged liver tissue. Therefore, silibinin represents a promising tool for the treatment of liver diseases. Since the silibinin molecule is insoluble in water and has poor bioavailability in vivo, new perspectives on solving this problem are being sought. The two most promising approaches are the water-soluble derivative silibinin-C-2',3-dihydrogen succinate, disodium salt, and the silibinin-phosphatidylcholine complex. Both drugs are currently under evaluation in liver disease clinical trials. Nevertheless, the mechanism underlying silibinin biological activity is still elusive and its more detailed understanding would undoubtedly increase its potential in the development of effective therapeutic strategies against liver diseases. This review is focused on the therapeutic potential of silibinin and its derivates, approaches to increase the bioavailability and the benefits in the treatment of liver diseases that have been achieved so far. The review discusses the relevant in vitro and in vivo studies that investigated the protective effects of silibinin in various forms of liver damage.

Silibinin is used to treat non-alcohol fatty liver disease (NAFLD) despite having rapid liver metabolism. Therefore, we investigated the role of the intestine in silibinin mechanism of action.

NAFLD mice model was established by feeding them with a high-fat diet (HFD). Liver pathological were examined using H&E and oil red O staining. Tissue distribution of silibinin was detected by LC-MS/MS. SiRNA was employed for gene silencing and plasmid was used for gene overexpression. ChIP-qPCR assay was performed to detect the levels of histone acetylation. Recombinant adeno-associated virus 9-short hairpin-fibroblast growth factor (FGF)-15 and -farnesoid X receptor (FXR; NR1H4) were used to knockdown expression of FGF-15 and FXR.

Oral silibinin significantly reversed NAFLD in mice, although liver concentration was insufficient for reduction of lipid accumulation in hepatocytes. Among endogenous factors capable of reversing NAFLD, the expression of Fgf-15 was selectively up-regulated by silibinin in ileum and colon of mice. When intestinal expression of Fgf-15 was knocked down, protection of silibinin against lipid accumulation and injury of livers nearly disappeared. Silibinin could reduce activity of histone deacetylase 2 (HDAC2), enhance histone acetylation in the promoter region of FXR and consequently increase intestinal expression of FGF-15/19.

Oral silibinin selectively promotes expression of FGF-15/19 in ileum by enhancing transcription of FXR via reduction of HDAC2 activity, and FGF-15/19 enters into circulation to exert anti-NAFLD action. As the site of action is the intestine this would explain the discrepancy between pharmacodynamics and pharmacokinetics of silibinin.

Oxidative stress is a key factor in the development of chronic diseases such as type 2 diabetes, cardiovascular diseases, and liver disorders. Antioxidant therapies that target oxidative damage show significant promise in preventing and treating these conditions. Berberine, an alkaloid derived from various plants in the Berberidaceae family, enhances cellular defenses against oxidative stress through several mechanisms. It activates the AMP-activated protein kinase (AMPK) pathway, which reduces mitochondrial reactive oxygen species (ROS) production and improves energy metabolism. Furthermore, it boosts the activity of key antioxidant enzymes like superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), thus protecting cells from oxidative damage. These actions make berberine effective in managing diseases like type 2 diabetes, cardiovascular conditions, and neurodegenerative disorders. Silymarin, a flavonolignan complex derived from Silybum marianum, is particularly effective for liver protection. It activates the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, enhancing antioxidant enzyme expression and stabilizing mitochondrial membranes. Additionally, silymarin reduces the formation of ROS by chelating metal ions, and it also diminishes inflammation. This makes it beneficial for conditions like non-alcoholic fatty liver disease (NAFLD) and alcohol-related liver disorders. This review aims to highlight the distinct mechanisms by which berberine and silymarin exert their antioxidant effects.

Extracts prepared from the seeds of the medicinal plant milk thistle [Silybum marianum (L.) Gaertn. (Asteraceae)] are widely used as dietary supplements due to anti-inflammatory, antitumor, and hepatoprotective effects. Called silymarin, the main components of lipophilic extracts of milk thistle seeds are flavonoids and flavonolignans including silybin A, silybin B, isosilybin A, isosilybin B, silydianin, silychristin, taxifolin, and 2,3-dehydrosilybins. The aim of this study was to develop a method based on UHPLC-MS/MS for the chemical authentication and standardization of milk thistle silymarin. Validation included the method of standard addition to account for the lack of a blank matrix. Potential matrix effects were investigated by analyzing silymarin standards dissolved only in the initial UHPLC mobile phase. Measurements of six flavonolignans and taxifolin in the milk thistle extract using UHPLC-MS/MS with standard addition or external standard calibration produced similar results for all analytes except silydianin and 2,3-dehydrosilybin B, which showed significant peak enhancement during negative ion electrospray due to botanical matrix effects. The UHPLC-MS/MS-based method of standard addition requires <10 min per injection and is suitable for the standardization of silymarin from milk thistle in support of preclinical and clinical studies of safety and efficacy.

Organic anion-transporting polypeptides (OATP) 1B1 and OATP1B3, encoded by the SLCO gene family of the solute carrier superfamily, are involved in the disposition of many exogenous and endogenous compounds. Preclinical rodent models help assess risks of pharmacokinetic interactions, but interspecies differences in transporter orthologs and expression limit direct clinical translation. An OATP1B transgenic mouse model comprising a rodent Slco1a/1b gene cluster knockout and human SLCO1B1 and SLCO1B3 gene insertions provides a potential physiologically relevant preclinical tool to predict pharmacokinetic interactions. Pharmacokinetics of exogenous probe substrates, pitavastatin and pravastatin, and endogenous OATP1B biomarkers, coproporphyrin-I and coproporphyrin-III, were determined in the presence and absence of known OATP/Oatp inhibitors, rifampin or silymarin (an extract of milk thistle [Silybum marianum]), in wild-type FVB mice and humanized OATP1B mice. Rifampin increased exposure of pitavastatin (4.6- and 2.8-fold), pravastatin (3.6- and 2.2-fold), and coproporphyrin-III (1.6- and 2.1-fold) in FVB and OATP1B mice, respectively, but increased coproporphyrin-I AUC0-24h only (1.8-fold) in the OATP1B mice. Silymarin did not significantly affect substrate AUC, likely because the silymarin flavonolignan concentrations were at or below their reported IC50 values for the relevant OATPs/Oatps. Silymarin increased the Cmax of pitavastatin 2.7-fold and pravastatin 1.9-fold in the OATP1B mice. The data of the OATP1B mice were similar to those of the pitavastatin and pravastatin clinical data; however, the FVB mice data more closely recapitulated pitavastatin clinical data than the data of the OATP1B mice, suggesting that the OATP1B mice are a reasonable, though costly, preclinical strain for predicting pharmacokinetic interactions when doses are optimized to achieve clinically relevant plasma concentrations.

Three-dimensional liver bioprinting is an emerging technology in the field of regenerative medicine that aids in the creation of functional tissue constructs that can be used as transplantable organ substitutes. During transplantation, the bioprinted donor liver must be protected from the oxidative stress environment created by various factors during the transplantation procedure, as well as from drug-induced damage from medications taken as part of the post-surgery medication regimen following the procedure. In this study, Silymarin, a flavonoid with the hepatoprotective properties were introduced into the GelMA bioink formulation to protect the bioprinted liver against hepatotoxicity. The concentration of silymarin to be added in GelMA was optimised, bioink properties were evaluated, and HepG2 cells were used to bioprint liver tissue. Carbon tetrachloride (CCl4) was used to induce hepatotoxicity in bioprinted liver, and the effect of this chemical on the metabolic activities of HepG2 cells was studied. The results showed that Silymarin helps with albumin synthesis and shields liver tissue from the damaging effects of CCl4. According to gene expression analysis, CCl4 treatment increased TNF-α and the antioxidant enzyme SOD expression in HepG2 cells while the presence of silymarin protected the bioprinted construct from CCl4-induced damage. Thus, the outcomes demonstrate that the addition of silymarin in GelMA formulation protects liver function in toxic environments.

It is suggested that supplementation with silymarin (SIL) has beneficial impacts on kidney and liver functions. This systematic review and dose-response meta-analysis assessed the impact of SIL administration on certain hepatic, renal, and oxidative stress markers. A systematic search was conducted in various databases to identify relevant trials published until January 2023. Randomized controlled trials (RCTs) that evaluated the effects of SIL on kidney and liver markers were included. A random-effects model was used for the analysis and 41 RCTs were included. The pooled results indicated that SIL supplementation led to a significant reduction in serum levels of alkaline phosphatase, alanine transaminase, creatinine, and aspartate aminotransferase, along with a substantial elevation in serum glutathione in the SIL-treated group compared to their untreated counterparts. In addition, there was a nonsignificant decrease in serum levels of gamma-glutamyl transferase, malondialdehyde (MDA), total bilirubin, albumin (Alb), total antioxidant capacity, and blood urea nitrogen. Sub-group analyses revealed a considerable decline in MDA and Alb serum values among SIL-treated participants with liver disease in trials with a longer duration (≥12 weeks). These findings suggest that SIL may ameliorate certain liver markers with potential hepatoprotective effects, specifically with long-term and high-dose supplementation. However, its nephroprotective effects and impact on oxidative stress markers were not observed. Additional high-quality RCTs with longer durations are required to determine the clinical efficacy of SIL supplementation on renal and oxidative stress markers.

Silybum marianum (L.) Gaertn., commonly known as milk thistle, is a medicinal plant belonging to the Asteraceae family. This plant has been recognized for its medicinal properties for over 2,000 years. However, the genome of this plant remains largely undiscovered, having no reference genome at a chromosomal level. Here, we assembled the chromosome-level genome of S. marianum, allowing for the annotation of 53,552 genes and the identification of transposable elements comprising 58% of the genome. The genome assembly from this study showed 99.1% completeness as determined by BUSCO assessment, while the previous assembly (ASM154182v1) showed 36.7%. Functional annotation of the predicted genes showed 50,329 genes (94% of total genes) with known protein functions in public databases. Comparative genome analysis among Asteraceae plants revealed a striking conservation of collinearity between S. marianum and C. cardunculus. The genomic information generated from this study will be a valuable resource for milk thistle breeding and for use by the larger research community.

Owing to the rich phytochemical content of Silymarin, it may effectively manage inflammation and oxidative stress. We, therefore, aimed to examine the existing evidence on the effect of Silymarin consumption on inflammation and oxidative stress factors by conducting a systematic review and meta-analysis of randomized controlled trials.

A systematic literature search up to September 2023 was completed in PubMed/Medline, Scopus, and Web of Science, to identify eligible RCTs. Heterogeneity tests of the selected trials were performed using the I2 statistic. Random effects models were assessed based on the heterogeneity tests, and pooled data were determined as weighted mean differences with a 95% confidence interval.

Fifteen RCTs were included in this meta-analysis. Our findings showed that Silymarin consumption significantly decreased CRP (WMD, - 0.50 mg/L; 95% CI, (- 0.95 to - 0.04); p = 0.03), MDA (WMD, - 1.19 nmol/mL; 95% CI, (- 1.99 to - 0.38); p = 0.004), and IL-6 (WMD, - 0.44 pg/ml; 95% CI, (- 0.75 to - 0.12); p = 0.006). Silymarin consumption had no significant effects on IL-10, TAC, and GSH. A significant non-linear relationship was observed between the duration of the intervention and MDA changes.

Silymarin can help reduce inflammation in patients with diabetes and thalassemia by reducing MDA as an oxidative stress marker and CRP and IL-6 as inflammatory markers.

It has been suggested that silymarin (SIL) supplementation has positive effects on cardiovascular health and reduces the risk of cardiometabolic syndrome (CMS). This systematic review and dose-response meta-analysis assessed the impacts of SIL administration on cardiovascular risk factors. A systematic search of multiple databases was performed to identify eligible controlled trials published up to January 2023. The analysis used a random-effects model and included 33 trials with 1943 participants. It was revealed that SIL supplementation led to a notable reduction in serum levels of fasting blood glucose (FBG) (weighted mean difference (WMD): -21.68 mg/dL, 95% CI: -31.37, -11.99; p < 0.001), diastolic blood pressure (DBP) (WMD: -1.25 mmHg; 95% CI: -2.25, -0.26; p = 0.013), total cholesterol (TC) (WMD: -13.97 mg/dL, 95% CI: -23.09, -4.85; p = 0.003), triglycerides (TG) (WMD: -26.22 mg/dL, 95% CI: -40.32, -12.12; p < 0.001), fasting insulin (WMD: -3.76 mU/mL, 95% CI: -4.80, -2.72; p < 0.001), low-density lipoprotein (LDL) (WMD: -17.13 mg/dL, 95% CI: -25.63, -8.63; p < 0.001), and hemoglobin A1C (HbA1c) (WMD: -0.85%, 95% CI: -1.27, -0.43; p < 0.001) in the SIL-treated groups compared to their untreated counterparts. In addition, there were no substantial differences in body mass index (BMI), systolic blood pressure (SBP), C-reactive protein (CRP), body weight, and high-density lipoprotein (HDL) between the two groups. These outcomes suggest that SIL consumption reduces certain CMS risk factors and has favorable impacts on lipid and glycemic profiles with potential hypotensive effects. These findings should be supported by additional trials with larger sample sizes and longer durations.

Hepatitis B virus (HBV)-related liver cirrhosis (HBV-LC) presents a substantial mortality and hepatocellular carcinoma (HCC) risk. While antiviral therapy (AVT) is the standard, complete HBV clearance remains elusive and may not reduce the risk of death in patients with decompensated cirrhosis. Silymarin, a centuries-old herbal remedy, has shown promise against HBV infection and as an antifibrosis therapy. This study explores the potential of silymarin combined with AVT to reduce mortality and HCC incidence in patients with HBV-LC. This research, spanning from 2001 to 2019, entailed a multi-institutional retrospective cohort study which included 8447 HBV-LC patients all undergoing AVT. After applying inclusion and exclusion criteria, the study comprised two cohorts: a case cohort receiving silymarin alongside AVT for at least 30 days, and a control cohort on AVT alone. Propensity score matching, based on baseline parameters including HBV-DNA levels, comorbidity, and an important LC medication, namely, non-selective β-blockers, was employed to ensure balanced groups, resulting in 319 patients in each cohort for subsequent analyses. Overall mortality was the primary outcome, with HCC occurrence as a secondary outcome. Among 319 patients in both cohorts, the case cohort exhibited significant improvements in the international normalized ratio (INR), model for end-stage liver disease (MELD) score and the Charlson comorbidity index (CCI) one year after the index date. A competing risk survival analysis demonstrated superior one-year and two-year mortality outcomes in the case cohort. However, no significant impact on one-year and two-year HCC occurrence was observed in either cohort. The combination of silymarin and AVT in HBV-LC patients demonstrated a synergistic effect, leading to decreased overall mortality and an improved comorbidity index. While the incidence of HCC remained unchanged, our results suggested promising potential for further clinical trials investigating the synergistic role of silymarin in the treatment of HBV-LC.

Introduction: Liver dysfunction is one of the most common disorders in patients with acute lymphoblastic leukemia (ALL). In recent studies, silymarin has been observed to have hepatic protective effects. Therefore, in this study, the effect of oral silymarin on the hepatic functions of patients with ALL was investigated. Methods: In the present double-blind clinical trial study, 121 patients with ALL over 5 years of age were divided into two groups after obtaining informed consent. The subjects were randomly divided into a silymarin-treatment group and a placebo group. In the silymarin-treatment group, patients received 70 mg oral capsules of silymarin twice daily or syrup of silymarin three times a day (each 5 ml of syrup contains 50 mg of silymarin). Patients were examined once a month for 9 months to receive capsules and measure the levels of alanine aminotransferase (ALT), aspartate transferase (AST), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), bilirubin, albumin, and cholesterol. Results: Comparison of changes before and after treatment in the two groups showed that receiving oral silymarin resulted in a slight significant decrease in the levels of ALT, AST, GGT, and bilirubin (p < 0.05), but had no effect on ALP, albumin, and cholesterol (p > 0.05). Discussion: The results of the present study showed that in pediatric patients with ALL, silymarin intake improves liver function. The very strong antioxidant effect of silymarin may explain its protective effect on the liver. Clinical Trial Registration: IRCT20150119020715N10.

Hepatitis C virus (HCV) infection is a significant global health concern, prompting the need for effective treatment strategies. This in-depth review critically assesses the landscape of HCV treatment, drawing parallels between traditional interferon/ribavirin therapy historically pivotal in HCV management and herbal approaches rooted in traditional and complementary medicine. Advancements in therapeutic development and enhanced clinical outcomes axis on a comprehensive understanding of the diverse HCV genome, its natural variations, pathogenesis, and the impact of dietary, social, environmental, and economic factors. A thorough analysis was conducted through reputable sources such as Science Direct, PubMed, Scopus, Web of Science, books, and dissertations. This review primarily focuses on the intricate nature of HCV genomes and explores the potential of botanical drugs in both preventing and treating HCV infections.

We report the first total synthesis of silybin A (1). Key synthetic steps include the construction of the 1,4-benzodioxane neolignan skeleton, a modified Julia-Kocienski olefination reaction between m-nitrophenyltetrazole sulfone (m-NPT sulfone) 10 and aldehyde 21, the formation of the flavanol lignan skeleton 28 via a quinomethide intermediate under acidic conditions, and stepwise oxidation of the benzylic position of flavanol 29.

Viral diseases have a significant impact on human health, and three novel coronaviruses (CoV) have emerged during the 21st century. In this review, we have emphasized the potential of herbal substances with antiviral effects. Our investigation focused on the features and prospects of viral disease treatment, with a particular emphasis on proinflammatory cytokines. We conducted comprehensive searches of various databases, including Science Direct, CABI Direct, Web of Science, PubMed, and Scopus. Cytokine storm mechanisms play a crucial role in inducing a pro-inflammatory response by triggering the expression of cytokines and chemokines. This response leads to the recruitment of leukocytes and promotes antiviral effects, forming the first line of defense against viruses. Numerous studies have investigated the use of herbal medicine candidates as immunomodulators or antivirals. However, cytokine-storm-targeted therapy is recommended for patients with acute respiratory distress syndrome caused by SARS-CoV to survive severe pulmonary failure. Our reviews have demonstrated that herbal formulations could serve as alternative medicines and significantly reduce complicated viral infections. Furthermore, they hold promising potential as specific antiviral agents in experimental animal models.

Reared rainbow trout are vulnerable to environmental stressors, in particular seasonal water warming, which affects fish welfare and growth and induces a temperature response, which involves modifications in tissue lipid profiles. Dietary supplements of plant origin, including the studied mix of a flavonoid, dihydroquercetin and a polysaccharide, arabinogalactan (25 and 50 mg per 1 kg of feed, respectively), extracted from larch wood waste, were shown to facilitate stress tolerance in fish and also to be beneficial for the safety of natural ecosystems and the sustainability of aquaculture production. This four-month feeding trial aimed to determine the effects of the supplement on liver and muscle lipid accumulation and the composition in rainbow trout reared under environmental variables. During periods of environmental optimum for trout, a consistent increase in energy lipid stores, particularly triacylglycerols (2.18 vs. 1.49-fold over a growing season), and an overall increase in lipid saturation due to lower levels of PUFAs, such as eicosapentaenoic (20:5n-3), docosahexaenoic (22:6n-3) and arachidonic (20:4n-6) acids, were observed in both control and supplement-fed fish, respectively. However, in fish stressed by an increase in ambient temperature, dietary supplementation with dihydroquercetin and arabinogalactan reduced mortality (3.65 in control vs. 2.88% in supplement-fed fish, p < 0.05) and alleviated the high-temperature-induced inhibition of lipid accumulation. It also stabilised the membrane phospholipid ratio and moderated the fatty acid composition of fish muscle and liver, resulting in higher levels of n-3 PUFAs and their precursors. Thus, the natural compounds tested are beneficial in accelerating fish tolerance to environmental stressors, reducing mortality and thermal response, and moderately improving fillet quality attributes by increasing the protein/lipid ratio and the abundance of fatty acids essential for human nutrition.

Parkinson's disease (PD) is the second most frequent neurodegenerative disease associated with motor dysfunction secondary to the loss of dopaminergic neurons in the nigrostriatal axis. Actual therapy consists mainly of levodopa; however, its long-term use promotes secondary effects. Consequently, finding new therapeutic alternatives, such as neuroprotective molecules, is necessary. Among these alternatives is silybin (Sb), the major bioactive flavonolignan in silymarin. Both exert neuroprotective effects, preserving dopamine levels and dopaminergic neurons when administered in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse PD model, being probably Sb the potential therapeutic molecule behind this effect. To elucidate the role of Sb in the PD model, we determined the dose-dependent conservation of striatal dopamine content following Sb oral administration. Then, we evaluated motor deficit tests using the best dopamine conservative dose of Sb and determined a cytokine-dependent inflammatory profile status, malondialdehyde as an oxidative stress product, and neurotrophic factors content in the MPTP-induced mouse PD model. Our results show that oral Sb at 100 mg/kg dose conserved about 60% dopamine levels. Also, Sb improved motor deficits, preserved neurotrophic factors content and mitochondrial function, reduced lipid peroxidation, diminished proinflammatory cytokines to basal levels, enhanced fractalkine production in the striatum and substantia nigra, and increased IL-10 and IL-4 levels in the substantia nigra in the MPTP mice. Thus, oral Sb may be a potential pharmacological PD treatment alternative.

Hepatitis C virus (HCV), a global malady, causes acute and chronic hepatitis leading to permanent liver damage, hepatocellular carcinoma, and death. Modern anti-HCV therapies are efficient, but mostly inaccessible for residents of underdeveloped regions. To innovate more effective treatments at affordable cost, medicinal plant-based products need to be explored. The aim of this article is to review plant constituents in the light of putative anti-HCV mechanisms of action, and discuss existing problems, challenges, and future directions for their potential application in therapeutic settings. One hundred sixty literatures were collected by using appropriate search strings via scientific search engines: Google Scholar, PubMed, ScienceDirect, and Scopus. Bibliography was prepared using Mendeley desktop software. We found a substantial number of plants that were reported to inhibit different stages of HCV life cycle. Traditional medicinal plants such as Phyllanthus amarus Schumach. and Thonn., Eclipta alba (L.) Hassk., and Acacia nilotica (L.) Delile exhibited strong anti-HCV activities. Again, several phytochemicals such as epigallocatechin-3-gallate, honokilol, punicalagin, and quercetin have shown broad-spectrum anti-HCV effect. We have presented promising phytochemicals like silymarin, curcumin, glycyrrhizin, and camptothecin for nanoparticle-based hepatocyte-targeted drug delivery. Nevertheless, only a few animal studies have been performed to validate the anti-HCV effect of these plant products. Again, insufficient clinical evaluation of the safety and effectiveness of herbal medications remain a problem. Selected plants products could be developed as novel therapeutics for HCV patients only after scrupulous evaluation of their safety and efficacy in a clinical set-up.

Aminoglycoside antibiotics and gentamicin (GN), in particular, are still widely used in clinical practice. It is a well-known fact that GN causes nephrotoxicity, and redox disturbances are discussed as a factor in its side effects. Recently, a new type of cell oxidative death, named ferroptosis, was discovered; it is associated with iron accumulation in the cell, glutathione (GSH) depletion and inactivation of glutathione peroxidase-4 (GPX4), reactive oxygen species (ROS) increment with concomitant lipid peroxidation. In this regard, a possible connection between GN-induced renal damage, ferroptosis and the overall antioxidant status of the organism could be investigated. Moreover, due to its beneficial effects, GN is still one of the main choices as a therapeutic agent for several diseases, and the possible reduction of its side effects with the application of certain antioxidants will be of important clinical significance. The study was conducted with adult male white mice divided into several groups (n = 6). GN nephrotoxicity was induced by the administration of GN 100-200 mg/kg i.p. for 10 days. The control group received only saline. The other groups received either Vitamin E (400 mg/kg p.o.) or Silymarin (200 mg/kg p.o.) applied alone or together with GN for the same period. After the end of the study, the animals were sacrificed, and blood and tissue samples were taken for the assessment of biochemical parameters and antioxidant status, as well as routine and specific for GPX4 histochemistry examination. The experimental results indicate that GN-induced nephrotoxicity negatively modulates GPX4 activity and is associated with increased production of ROS and lipid peroxidation. The groups treated with antioxidants demonstrated preserved antioxidant status and better GPX4 activity. In conclusion, the inhibition of ROS production and especially the suppression of ferroptosis, could be of clinical potential and can be applied as a means of reducing the toxic effects of GN application.

One of the biggest factors that negatively affect the cancer treatment plan is the toxic effects of chemotherapeutics on non-target cells and tissues. This information prompted us to investigate the protective effects of silymarin (SL), a hepatoprotective agent, against the hepatotoxic effects of the anticancer drug paclitaxel (PAC). Four groups were formed from 28 rats as control, PAC (2 mg/kg), SL (100 mg/kg) and PAC + SL (combination of PAC with SL). After completing the experimental procedures, the tissues collected after anesthesia were analyzed by Western blot, qRT-PCR, biochemical, stereological, immunohistochemical, and histopathological techniques. Administration of PAC significantly increased the expression of tumor necrosis factor-alpha (TNF-α), Bax, cytochrome-c (cyt-c), and active caspase-3, as well as malondialdehyde (MDA) levels in liver tissue and decreased glutathione (GSH) levels compared with the control group. PAC also resulted in a significant increase in serum triglyceride (TG), cholesterol (CH), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels compared with the control group. Pathological changes such as microvesicular steatosis, the formation of Councilman bodies, an increase in total sinusoidal volume, and a decrease in the total number of hepatocytes were observed in the liver tissue of the PAC group. Almost all analysis results in the PAC + SL group were similar to those in the control group, and no significant pathological alterations were observed in this group. The data obtained show that SL protects the liver from the harmful effects of PAC, especially thanks to its TNF-α suppressor, anti-inflammatory, anti-apoptotic and antioxidant effects. Based on this result, in cases where PAC is used in cancer treatment, it can be recommended to be used together with SL to prevent harmful effects on healthy liver tissue and to continue treatment uninterruptedly and effectively.

Taxifolin is a flavonoid compound, originally isolated from the bark of Douglas fir trees, which is often found in foods such as onions and olive oil, and is also used in commercial preparations, and has attracted the interest of nutritionists and medicinal chemists due to its broad range of health-promoting effects. It is a powerful antioxidant with excellent antioxidant, anti-inflammatory, anti-microbial and other pharmacological activities. This review focuses on the breakthroughs in taxifolin for the treatment of diseases from 2019 to 2022 according to various systems of the human body, such as the nervous system, immune system, and digestive system, and on the basis of this review, we summarize the problems of current research and try to suggest solutions and future research directions.

Natural feed supplements have been shown to improve fish viability, health, and growth, and the ability to withstand multiple stressors related to intensive cultivation. We assumed that a dietary mix of plant-origin substances, such as dihydroquercetin, a flavonoid with antioxidative, anti-inflammatory, and antimicrobial properties, and arabinogalactan, a polysaccharide with immunomodulating activity, would promote fish stress resistance and expected it to have a protective effect against infectious diseases. Farmed rainbow trout fish, Oncorhynchus mykiss, received either a standard diet or a diet supplemented with 25 mg/kg of dihydroquercetin and 50 mg/kg of arabinogalactan during a feeding season, from June to November. The fish in the control and experimental groups were sampled twice a month (eight samplings in total) for growth variable estimations and tissue sampling. The hepatic antioxidant status was assessed via the quantification of molecular antioxidants, such as reduced glutathione and alpha-tocopherol rates, as well as the enzyme activity rates of peroxidase, catalase, and glutathione-S-transferase. The lipid and fatty acid compositions of the feed and fish liver were analyzed using thin-layer and high-performance liquid chromatography. The viability, size, and biochemical indices of the fish responded to the growth physiology, environmental variables such as the dissolved oxygen content and water temperature, and sporadic factors. Due to an outbreak of a natural bacterial infection in the fish stock followed by antibiotic treatment, a higher mortality rate was observed in the fish that received a standard diet compared to those fed supplemented feed. In the postinfection period, reduced dietary 18:2n-6 and 18:3n-3 fatty acid assimilation contents were detected in the fish that received the standard diet in contrast to the supplemented diet. By the end of the feeding season, an impaired antioxidant response, including reduced glutathione S-transferase activity and glutathione content, and a shift in the composition of membrane lipids, such as sterols, 18:1n-7 fatty acid, and phospholipids, were also revealed in fish fed the standard diet. Dietary supplementation with plant-origin substances, such as dihydroquercetin and arabinogalactan, decreases lethality in fish stocks, presumably though the stimulation of natural resistance in farmed fish, thereby increasing the economic efficacy during fish production. From the sustainable aquaculture perspective, natural additives also diminish the anthropogenic transformation of aquaculture-bearing water bodies and their ecosystems.

This study aimed to develop a solid dispersion formulation of silymarin (Silymarin-SD) using freeze-drying method to enhance its oral bioavailability (BA) by inhibiting the intestinal first-pass effect and increasing its solubility and permeability. Silymarin-SD formulation (i.e., silymarin:tween 80:hydroxypropyl cellulose (HPC) = 1:1:3 (w/w/w) significantly increased silymarin permeability in the duodenum, jejunum, and ileum by decreasing the efflux ratio of silymarin and by inhibiting silymarin-glucuronidation activity, in which tween 80 played a crucial role. As a result, orally administered Silymarin-SD formulation increased plasma silymarin concentrations and decreased silymarin-glucuronide in rats compared with silymarin alone and silymmarin:D-α-tocopherol polyethylene glycol 1000 succinate (1:1, w/w) formulation. In addition to modulating intestinal first-pass effect, Silymarin-SD formulation showed a significantly higher cumulative dissolution for 120 min compared with that of silymarin from the physical mixture (PM) of the same composition as Silymarin-SD and silymarin alone; the relative BA of silymarin-SD increased to 215% and 589% compared with silymarin-PM and silymarin alone, respectively. This could be attributed to the amorphous status of the Silymarin-SD formulation without chemical interaction with excipients, such as tween 80 and HPC. Moreover, the hepatoprotective effect of Silymarin-SD in acetaminophen-induced acute hepatotoxicity, as estimated from the alanine aminotransferase and aspartate aminotransferase values, was superior to that of silymarin. In conclusion, the increase in the dissolution rate and intestinal permeability of silymarin, and the inhibition of silymarin-glucuronidation by the Silymarin-SD formulation, prepared using tween 80 and HPC, increased its plasma concentration and resulted in a superior hepatoprotective effect compared to silymarin.

This work reports the application of Gas Expanded Liquid (GXL) extraction to concentrate the flavonolignan fraction (silymarin) and taxifolin from Silybum marianum seeds, which have proven to be highly valuable health-promoting compounds. GXL using green solvents was used to isolate silymarin with the objective of replacing conventional methods. In one hand, the effect of different compositions of solvents, aqueous ethanol (20%, 50% or 80% (v/v)) at different CO2/liquid (25, 50 and 75%) ratios, on the GXL extraction was investigated. The obtained extracts have been chemically and functionally characterized by means of UHPLC-ESI-MS/MS (triple quadrupole) and in-vitro assays such as anti-inflammatory, anti-cholinergic and antioxidant. Results revealed that the operating conditions influenced the extraction yield, the total phenolic content and the presence of the target compounds. The best obtained yield was 55.97% using a ternary mixture of solvents composed of CO2:EtOH:H2O (25:60:15) at 40 °C and 9 MPa in 160 min. Furthermore, the results showed that obtained extracts had significant antioxidant and anti-inflammatory activities (with best IC50 value of 8.80 µg/mL and 28.52 µg/mL, respectively) but a moderate anti-cholinesterase activity (with best IC50 value of 125.09 µg/mL). Otherwise, the concentration of silymarin compounds in extract can go up to 59.6% using the present one-step extraction method without further purification, being silybinA+B the predominant identified compound, achieving value of 545.73 (mg silymarin/g of extract). The obtained results demonstrate the exceptional potential of GXL to extract high-added values molecules under sustainable conditions from different matrices.

Silymarin is found in Silybum marianum. We investigated the effect of silymarin on muscle atrophy in obese mice. The experimental mice were divided into three groups: CON, normal diet; HFD, 60% high-fat diet (HF); and SILY: 50 mg silymarin +60% HF. It was confirmed that increases in body weight and fat mass in the SILY group were significantly inhibited. Moreover, the muscle mass in SILY mice was significantly higher than that in the HFD group. The grip strength in HFD group was significantly reduced, whereas in the SILY group it was higher than that in HFD group. In HFD mice, the mRNA levels of protein degradation factors (muscle ring-finger protein 1 [MuRF-1] and Atrogin-1) were increased and protein synthesis factors (phosphoinositide 3-kinase [PI3K] and Akt) were decreased. However, silymarin was found to elevate the degradation factors as compared with HFD group, whereas it reduced the synthesis factors. The results suggest that silymarin could prevent not only obesity but also muscle atrophy.

Ratiometric fluorescent probes could effectively offset the changes of the autofluorescence and compartmental localization. FRET, ICT, etc. are the common strategies to design probes for biosensing, but these strategies have some deficiencies. Here, we proposed a new design strategy based on π-conjugation modulation, giving two different emission bands in the absence and presence of the target. The new fluorescence probe named Rhod-DCM-B was rationally designed and synthesized, which displayed a fluorescence emission peak at 670 nm because the electron cloud focuses on the conjugated DCM unit. With the addition of ONOO^-, the fluorescence emission at 570 nm increased, accompanied by the decrease of fluorescence emission at 670 nm, showing a ratiometric signal change attributed to the opened spirane structure making the electron cloud concentrated on the xanthene core. The mechanism is well confirmed by MS and DFT calculations. Rhod-DCM-B exhibited outstanding sensitivity and excellent selectivity toward ONOO^-. Moreover, Rhod-DCM-B was effectively employed to determine endogenous and exogenous ONOO^- in living cells. As a marker for inflammation and drug-induced liver injury (DILI) process, ONOO^- in vivo was successfully monitored by Rhod-DCM-B and presented a dramatic ratiometric response.

The factors (environmental and genetic) contributing to basal cell carcinoma (BCC) pathogenesis are well-established; however, effective agents for BCC prevention are marred by toxic side-effects. Herein, we assessed the efficacy of flavonolignan silibinin against ultraviolet B (UVB)-induced BCC in Ptch+/- (heterozygous patched homolog 1 gene) mouse model. Both male and female Ptch+/- mice were irradiated with a 240 mJ/cm2 UVB dose 3 times/week for 26 or 46 weeks, with or without topical application of silibinin (9 mg/200 µl in acetone, applied 30 min before or after UVB exposure). Results indicated that silibinin application either pre- or post-UVB exposure for 26 weeks significantly decreased the number of BCC lesions by 65% and 39% (P < 0.001 for both) and the area covered by BCCs (72% and 45%, P < 0.001 for both), respectively, compared to UVB alone. Furthermore, continuous UVB exposure for 46 weeks increased the BCC lesion number and the BCC area covered by ~6 and ~3.4 folds (P < 0.001), respectively. Notably, even in this 46 week prolonged UVB exposure, silibinin (irrespective of pre- or post-UVB treatment) significantly halted the growth of BCCs by 81-94% (P < 0.001) as well as other epidermal lesions; specifically, silibinin treated tissues had less epidermal dysplasia, fibrosarcoma, and squamous cell carcinoma. Immunohistochemistry and immunofluorescence studies revealed that silibinin significantly decreased basal cell proliferation (Ki-67) and the expression of cytokeratins (14 and 15), and Hedgehog signaling mediators Smo and Gli1 in the BCC lesions. Together, our findings demonstrate strong potential of silibinin to be efficacious in preventing the growth and progression of UVB-induced BCC.

Cystic echinococcosis (CE), is a parasitic zoonosis caused by Echinococcus granulosus (E. granulosus) larvae in liver and lungs of both humans and animals. Surgical intervention is the mainstay for CE treatment, using scolicidal agents that inactivate live protoscolices. This study evaluated the scolicidal effects of Silybum marianum ethanolic extract and its combination with albendazole in vitro for the first time. Moreover, in a literature review, we investigated the effects of a wide range of Iranian medicinal plants on protoscolices of E. granulosus.

S. marianum ethanolic extract was prepared and high-performance liquid chromatography (HPLC) analysis was used to establish the proportions of its component compounds in the extract. Cytotoxicity was evaluated in mouse macrophage cells (J774A.1 cell line) using MTT method. Next, the scolicidal activity of the extract alone and combined with albendazole was tested as triplicate at various concentrations incubated for 5, 10, 20, 30, and 60 min. Finally, protoscolex viability was determined using 0.1% eosin as a vital stain. PCR-RFLP and DNA sequencing techniques were used to characterize the genotype of E. granulosus.

HPLC analysis showed that S. marianum ethanolic extract contained mostly silydianin (14.41%), isosilybin A (10.50%), and silychristin (10.46%). The greatest scolicidal effects were obtained with the combination of S. marianum with albendazole (79%), S. marianum ethanolic extract alone (77%) and albendazole (69%), at a concentration of 500 μg/ml for 60 min, respectively (P < 0.05). Molecular analysis showed that all the cysts used were G1 genotype.

The data suggest that S. marianum ethanolic extract is a potential scolicide in vitro; however, further investigations are required to determine its efficacy in vivo.

Taxifolin, also known as dihydroquercetin, possesses several interesting biological properties. The purpose of the study was to identify polymorphs of taxifolin prepared using crystallization in different solvents. Data from X-ray powder diffraction, differential scanning calorimetry, and thermogravimetry enabled us to detect six different crystalline phases for taxifolin. Besides the already known fully hydrated phase, one partially hydrated phase, one monohydrated phase, two anhydrous polymorphs, and one probably solvated phase were obtained. The unit cell parameters were defined for three of them, while one anhydrous polymorph was fully structurally characterized by X-ray powder diffraction data. Scanning electron microscopy and hot stage microscopy were also employed to characterize the crystallized taxifolin powders. The hydrate and anhydrous forms showed remarkable stability in drastic storage conditions, and their solubility was deeply evaluated. The anhydrous form converted into the hydrate form during the equilibrium solubility study and taxifolin equilibrium solubility was about 1.2 mg/mL. The hydrate taxifolin intrinsic dissolution rate was 56.4 μg cm^-2 min^-1. Using Wood's apparatus, it was not possible to determine the intrinsic dissolution rate of anhydrous taxifolin that is expected to solubilize more rapidly than the hydrate form. In view of its high stability, its use can be hypothesized.

The pharmacological characteristics of phytochemicals have prompted a lot of interest in their application in disease management. Due to the high incidence of cancer related mortality and morbidity throughout the world; experiments have concentrated on identifying the anticancer potential of natural substances. Many phytochemicals such as flavonoids and their derivatives produced from food offer a variety of new anti-cancer agents which prevent the cancer progression. Taxifolin, a unique bioactive flavonoid, is a dietary component that has grabbed the interest of dietitians and medicinal chemists due to its wide range of health benefits. It is a powerful antioxidant with a well-documented effect in the prevention of several malignancies in humans. Taxifolin has shown promising inhibitory activity against inflammation, malignancies, microbial infection, oxidative stress, cardiovascular disease, and liver disease. Anti-cancer activity has been shown to be relatively significant than other activities investigated in vitro and in vivo with a little or no side effects to the normal healthy cells. In summary this review offers the synopsis of recent breakthroughs in the use of taxifolin as a cancer treatment, as well as mechanisms of action. However, to develop a medicine for human usage, more study on pharmacokinetic profile, profound molecular mechanisms, and drug safety criteria should be conducted utilizing well-designed randomized clinical trials.

COVID-19 pandemic, the most unprecedented event of the year 2020, has brought millions of scientists worldwide in a single platform to fight against it. Though several drugs are now in the clinical trial, few vaccines available on the market already but the lack of an effect of those is making the situation worse.

In this review, we demonstrated comprehensive data of natural antiviral products showing activities against different proteins of Human Coronaviruses (HCoV) that are responsible for its pathogenesis. Furthermore, we categorized the compounds into the hit, lead, and drug based on the IC50/EC50 value, drug-likeness, and lead-likeness test to portray their potentiality to be a drug. We also demonstrated the present status of our screened antiviral compounds with respect to clinical trials and reported the lead compounds that can be promoted to clinical trial against COVID-19.

A systematic search strategy was employed focusing on Natural Products (NPs) with proven activity (in vitro, in vivo, or in silico) against human coronaviruses, in general, and data were gathered from databases like PubMed, Web of Science, Google Scholar, SciVerse, and Scopus. Information regarding clinical trials retrieved from the Clinical Trial database.

Total "245" natural compounds were identified initially from the literature study. Among them, Glycyrrhizin, Caffeic acid, Curcumin is in phase 3, and Tetrandrine, Cyclosporine, Tacrolimus, Everolimus are in phase 4 clinical trial. Except for Glycyrrhizin, all compounds showed activity against COVID-19.

In summary, our demonstrated specific small molecules with lead and drug-like capabilities clarified their position in the drug discovery pipeline and proposed their future research against COVID-19.

Plant-based polyphenols are natural compounds, present in fruits and vegetables. During recent years, polyphenols have gained special attention due to their nutraceutical and pharmacological activities for the prevention and treatment of human diseases. Nevertheless, their photosensitivity and low bioavailability, rapid metabolism and short biological half-life represent the major limitations for their use, which could be overcome by polyphenols encapsulation (flavonoids and non-flavonoids) into chitosan (CS)-tripolyphosphate (TPP) based nanoparticles (NP). In this review, we particularly focused on the ionic gelation method for the NP design. This contribution exhaustively discusses and compares results of scientific reports published in the last decade referring to ionic gelation applied for the protection, controlled and site-directed delivery of polyphenols. As a consequence, CS-TPP NP would constitute true platforms to transport polyphenols, or a combination of them, to be used for the designing of a new generation of drugs or nutraceuticals.

This review focuses on the specific biological effects of optically pure silymarin flavo-nolignans, mainly silybins A and B, isosilybins A and B, silychristins A and B, and their 2,3-dehydro derivatives. The chirality of these flavonolignans is also discussed in terms of their analysis, preparative separation and chemical reactions. We demonstrated the specific activities of the respective diastereomers of flavonolignans and also the enantiomers of their 2,3-dehydro derivatives in the 3D anisotropic systems typically represented by biological systems. In vivo, silymarin flavonolignans do not act as redox antioxidants, but they play a role as specific ligands of biological targets, according to the "lock-and-key" concept. Estrogenic, antidiabetic, anticancer, antiviral, and antiparasitic effects have been demonstrated in optically pure flavonolignans. Potential application of pure flavonolignans has also been shown in cardiovascular and neurological diseases. Inhibition of drug-metabolizing enzymes and modulation of multidrug resistance activity by these compounds are discussed in detail. The future of "silymarin applications" lies in the use of optically pure components that can be applied directly or used as valuable lead structures, and in the exploration of their true molecular effects.

Flavonolignans, for example, silymarin and silybin, have interesting biological activities. For the first time, three new flavonolignans named oenanthenoid A-C (1-3) and nine known flavonolignan derivatives (4-12) were isolated from Oenanthe javanica. Comprehensive spectroscopic data analysis and references were used to identify all of the compounds. The anti inflammatory activities of these isolates (1-12) on RAW264.7 macrophage cells were investigated. Three new compounds (1-3) demonstrated anti inflammatory activity with IC₅₀ values ranging from 6.5 ± 0.6 to 14.7 ± 1.6 µM. Furthermore, two compounds (11 and 12) demonstrated moderate anti inflammatory activity, with IC₅₀ values ranging from 24.1 ± 1.2 to 62.5 ± 1.9 µM.

To identify the bioactive hepatoprotective components of the ethanol extract of Pentaclethra macrophylla stem bark using in vitro and in vivo approaches.

The bioguided-fractionation of the ethanol extract was based on the substances' capacity to prevent in vitro, the lipid peroxidation of hepatocytes' membranes induced by hydrogen peroxide. For the in vivo hepatoprotective test, mice were treated orally with the ethyl acetate (EtOAc) fraction of the ethanol extract at doses of 50 and 75 mg/kg/day for one week and subjected to d-galactosamine/lipopolysaccharide (GaIN/LPS)-induced hepatotoxicity. Blood samples were collected for alanine aminotransferase (ALAT), aspartate aminotransferase (ASAT), TNF-α and IL-1β assays. The liver was harvested for histological and biochemical (proteins, glutathione (GSH), catalase and superoxide dismutase (SOD)) analysis.

The ethanol extract and fractions induced concentration-dependent inhibition of lipid peroxidation (IC50: 3.21-48.90 μg/mL) greater than that of silymarin (IC50: 117.4 μg/mL). The purification of the sub-fractions of EtOAc fraction yielded: (7R)-7-hydroxyhexacosanoic acid (1), (7R)-1-(7-hydroxyhexacosanoyl) glycerol (2), bergenin (3), 11-O-galloylbergenin (4), 2-hydroxymethyl-5-(2-hydroxypropan-2-yl)phenol (5), β-sitosterol 3-O-β-d-glucopyranosyl (6) and β-sitosterol (7)), among which 11-O-galloylbergenin (IC50:1.8 μg/mL) was the most effective. The EtOAc fraction significantly reduced the serum level of ALAT, ASAT and TNF-α in vivo. This EtOAc fraction increased the liver protein content and protected the liver against structural damages, but did not boost the endogenous antioxidant parameters.

The stem bark of Pentaclethra macrophylla possesses hepatoprotective effects that may result from its capacity to inhibit lipid peroxidation and could be attributed to its active components 3, 4 and 2.

Polygoni Orientalis Fructus (POF) is a clinically effective Chinese medicine. Raw POF (RPOF) and POF Tostus (POFT) are used separately in clinics. However, incomplete progress has been made on quality control.

To establish a comprehensive method for quality assessment of RPOF and POFT and to discriminate these two varieties.

High-performance liquid chromatography combined with the diode array detector (HPLC-DAD) methods were developed for fingerprinting and quantitative analysis of seven major compounds in RPOF and POFT, and the main components were determined by HPLC-DAD coupled with Fourier-transform ion cyclotron resonance-mass spectrometry. Chemometric approaches were performed to discriminate RPOF and POFT and to screen discriminatory components.

Fingerprints were established and 12 common peaks were identified, cannabisin G and cannabisin E were firstly identified from POF. In quantitative analysis, all analytes showed good regression (R > 0.9996) within test ranges and the recovery of the method was in the range 96.6-104.3%. Fingerprints in conjunction with similarity analysis and hierarchical clustering analysis (HCA) demonstrated the consistent quality of RPOF and showed a clear discrimination between RPOF and POFT. Principal component analysis, partial least-squares discriminant analysis, and heatmap-HCA on quantitative data not only gave a clear differentiation between RPOF and POFT, but they also suggested that quercetin, 3,5,7-trihydroxychromone, and N-trans-feruloyltyramine acted as the main factors responsible for the sample differences.

Chromatographic analysis in combination with chemometric analysis provides a simple and reliable method of comparing and evaluating the qualities of RPOF and POFT.

Taxifolin (3,5,7,3,4-pentahydroxy flavanone or dihydroquercetin, Tax) was identified as a gastroprotective compound and a gastroadhesive formulation was recently developed to prolong its residence time and release in the stomach. So, the gastric healing effectiveness of Tax and gastro-mucoadhesive microparticles containing Tax (MPTax) against the acetic acid induced-gastric ulcer in rats was investigated in this study. Moreover, the interactions between Tax and H⁺/K⁺-ATPase were investigated in silico, and its anti- H. pylori activity was determined in vitro. The oral treatment with MPTax (81.37 mg/kg, containing 12.29% of Tax) twice a day for seven days reduced the ulcer area by 63%, compared to vehicle-treated group (Veh: 91.9 ± 10.3 mm²). Tax (10 mg/kg, p.o) reduced the ulcer by 40% but with a p = 0.07 versus Veh group. Histological analysis confirmed these effects. Tax and MPTax increased the gastric mucin amount, reduced the myeloperoxidase activity, and increased the glutathione reduced content at ulcer site. However, only MPTax decreased the lipoperoxide accumulation at ulcer site. Besides, Tax and MPTax normalize the catalase and glutathione S-transferase activity. Tax showed reversible interaction with H⁺/K⁺-ATPase in silico and its anti-H. pylori effects was confirmed (MIC = 625 μg/mL). These results suggest that the antiulcer property of Tax involves the strengthening of the gastric protective factors in parallel to its inhibitory interaction with H⁺/K⁺-ATPase and H. pylori. Considering that ulcer healing action displayed by Tax was favored by gastroadhesive microparticles, this approach seems to be promising for its oral delivery to treat acid-peptic diseases.