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Background: Osteosarcoma (OS) is the most common primary malignancy in bone tissues, and effective therapeutics remain absent in clinical practice. Traditional Chinese medicines (TCM) have been used for thousands of years, which provide great insights into OS management. Gallic acid (GA) is a natural phenolic acid enriched in various foods and herbs. Several pharmacological activities of GA such as anti-oxidation and anti-inflammation have been well-established. However, its biological function in OS remains not fully understood., Methods: The potential anti-cancer properties of GA were evaluated in 143 ​B, U2OS and MG63 ​cells. Its effects on cell growth, cell cycle, apoptosis and migration were examined in these OS cells. The lncRNA H19 and Wnt/β-catenin signaling were detected by qPCR, luciferase activity and Western blotting assays. The in vivo effect of GA on tumor growth was investigated using an orthotopic mouse model., Results: In the present study, GA was found to suppress the tumor growth in vitro via inducing cell cycle arrest and apoptosis in OS cells, and inhibit the invasion and metastasis as well. Using the orthotopic animal model, GA was also found to suppress tumorigenesis in vivo . Long noncoding RNA (lncRNA) H19 was demonstrated to be down-regulated by GA, and thus disrupted the canonical Wnt/β-catenin signaling in OS cells. Furthermore, the ectopic expression of H19 rescued the GA-induced suppressive effects on tumor growth and metastasis, and partially reversed the inactivation of Wnt/β-catenin signaling., Conclusions: Taken together, our results indicated that GA inhibited tumor growth through an H19-mediated Wnt/β-catenin signaling regulatory axis in OS cells., The Translational Potential of This Article: The information gained from this study provides a novel underlying mechanism of GA mediated anti-OS activity, suggesting that GA may be a promising drug candidate for OS patients., Competing Interests: A conflict of interest occurs when an individual’s objectivity is potentially compromised by a desire for financial gain, prominence, professional advancement or a successful outcome. The Editors of the Journal of Orthopaedic Translation strive to ensure that what is published in the Journal is as balanced, objective and evidence-based as possible. Since it can be difficult to distinguish between an actual conflict of interest and a perceived conflict of interest, the Journal requires authors to disclose all and any potential conflicts of interest., (© 2022 The Authors.)

Green tea processed from albino tea varieties often has umami taste and fresh aroma. This study identified green teas made from two types of albino tea cultivar, one having the white shoots (called Naibai, NB) and the other having the yellow shoots (called Huangjinya, HJY). Taste compounds analyses showed that galloylated catechins were highly concentrated in HJY green teas, whereas non-galloylated catechins and amino acids were more abundant in NB green teas. CsTA (involved in the catabolism of galloylated catechins) showed high expression in HJY tea shoots, resulting in gallic acid as a precursor for β -glucogallin biosynthesis being abundant in HJY. CsPDX2.1 (responsible for theanine hydrolyzation) had a lower expression level in NB than HJY shoots. Fatty acid-derived volatiles (FADVs), glycosidically bound volatiles (GBVs) and carotenoid-derived volatiles (CDVs) were highly concentrated in HJY green teas, whereas amino acids-derived volatiles were highly concentrated in NB green teas., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Ziziphus abyssinica root bark is widely used in folk medicine to manage liver diseases, particularly, jaundice but its effect on paracetamol-induced liver toxicity (PILT) has not yet been validated. This study explored the ameliorative effect of ethanolic root bark extract of Ziziphus abyssinica (ZAE) against PILT in rats. The flavonoid and phenolic content of ZAE was evaluated using Folin-Ciocalteau and aluminium trichloride colorimetric methods, respectively. Antioxidant activity of ZAE was determined in vitro by evaluating its ferrous reducing antioxidant capacity (FRAC) as well as DPPH and nitic oxide (NO) radicals scavenging activities. Sprague-Dawley rats were assigned to six groups (n = 6) and administered with normal saline (10 mL/kg, p.o .), N-acetylcysteine (50 mg/kg, i.p.) and ZAE (30, 100, and 300 mg/kg, p.o .) respectively for seven days after which they received paracetamol (PCM, 3000 mg/kg, p.o .). Animals were sacrificed 48 h after paracetamol administration under light anaesthesia and assessed for liver toxicity and oxidative stress. Total flavonoid and phenolic contents of ZAE were 1313.425 µg/mL quercetin equivalence and 268.31 µg/mL gallic acid equivalence respectively. ZAE exhibited marked FRAC as well as DPPH and NO radical scavenging activities with IC 50 s of 80.41 ± 1.56, 67.56 ± 1.11 and 7.11 ± 1.48 μg/mL respectively. ZAE and N-acetylcysteine significantly ( p  < 0.05) reduced the paracetamol-mediated elevation of serum total bilirubin, proteins and activity of liver enzymes (AST, ALP, and ALT). Similarly, ZAE increased hepatic glutathione, total thiols and catalase activity of the paracetamol intoxicated rats. Morphological changes associated with the paracetamol hepatotoxicity were also ameliorated by ZAE. Overall, the hepatoprotective effect of ZAE may be related to its antioxidant property., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Common treatments for the management of diabetes have limitations due to side effects, hence the need for continuous research to discover new remedies with better therapeutic efficacy. Previously, we have reported that the combination treatment of gallic acid (20 mg/kg) and andrographolide (10 mg/kg) for 15 days demonstrated synergistic hypoglycemic activity in the streptozotocin (STZ)-induced insulin-deficient diabetes rat model. Here, we attempt to further elucidate the effect of this combination therapy at the biochemical, histological and molecular levels. Our biochemical analyses showed that the combination treatment significantly increased the serum insulin level and decreased the total cholesterol and triglyceride level of the diabetic animals. Histological examinations of H&E stained pancreas, liver, kidney and adipose tissues of combination-treated diabetic animals showed restoration to the normalcy of the tissues. Besides, the combination treatment significantly enhanced the level of glucose transporter-4 (GLUT4) protein expression in the skeletal muscle of treated diabetic animals compared to single compound treated and untreated diabetic animals. The molecular docking analysis on the interaction of gallic acid and/or andrographolide with the adiponectin receptor 1 (AdipoR1), a key component in the regulation of pancreatic insulin secretion, revealed a greater binding affinity of AdipoR1 to both compounds compared to individual compounds. Taken together, these findings suggest the combination of gallic acid and andrographolide as a potent therapy for the management of diabetes mellitus., Competing Interests: The authors want to declare that they have no conflict of interest associated with this publication., (© 2022 Center for Food and Biomolecules, National Taiwan University. Production and hosting by Elsevier Taiwan LLC.)

Ethyl acetate extracts of seeds originating from nine Hellenic native and international Vitis vinifera varieties cultivated in Greece were screened for their contents of characteristic polyphenols. The compounds determined were principal constituents of low molecular weight, including gallic acid (GA), catechin (CT), epicatechin (ECT), epigallocatechin (EGC), epicatechin gallate (ECG), epigallocatechin gallate (EGCG), and the procyanidins B1 and B2 (dimers). Total content varied from 55.1 to 964 mg per 100 g of seeds, the average being 380 mg per 100 g. The most abundant polyphenol was CT, accounting for 49.8% of the total content, followed by ECT (26.0%), ECG (9.3%), procyanidin B1 (5.8%), and procyanidin B2 (5.1%), whereas EGC and GA were minor constituents. The assessment of the in vitro antiradical activity (AAR), employing the stable radical DPPH⋅, showed that there is a significant correlation with total polyphenol content (r2=0.6499, P<0.01). The correlations with the individual compounds, however, revealed that procyanidin B1 may be one of the most important radical scavengers in grape seed extracts (r2=0.7934, P<0.002), despite its low contribution to the overall polyphenol content. [Copyright &y& Elsevier]

We have recently established that the blood concentrations of gallic acid (GA), a polyphenolic component naturally found in food, and its O-methyl derivatives are very low (practically ⩽1 μM) in physiological (postprandial) condition. Using acellular oxidant systems and macrophage-differentiated promonocytes (MDPs) THP-1, we show here that the direct and indirect (through depressing effect on the superoxide cell production) antioxidant properties of these components were not effective at these concentrations. In contrast, 4-O-methyl GA was the most efficient component to depress AT1R and CD36 mRNA expression in Ang II-treated MDPs, suggesting a strong inhibition of Ang II-triggered pro-atherogenic mechanisms of foam cell formation. [Copyright &y& Elsevier]

Antioxidative effects of the principal polyphenolic components extracted from green tea leaves, i.e. (−)-epicatechin (EC), (−)-epicatechin gallate (ECG), (−)-epigallocatechin gallate (EGCG), (−)-epigallocatechin (EGC), and gallic acid (GA), against free radical initiated peroxidation of rat liver microsomes were studied. The peroxidation was initiated by a water-soluble azo compound 2,2′-azobis(2-amidinopropane hydrochloride (AAPH). The reaction kinetics was monitored by oxygen uptake and formation of malondialdehyde (MDA). Kinetic analysis of the antioxidation process demonstrates that these green tea polyphenols (GOHs), especially EC and ECG which bear ortho-dihydroxyl functionality, are good antioxidants for microsomal peroxidation. The antioxidant synergism of these GOHs with the endogenous α-tocopherol (TOH) (vitamin E) is also discussed. [Copyright &y& Elsevier]

Gallic acid (GA) is a natural polyphenolic compound with many health benefits. To assess the potential risk of long-term consumption of GA to gut health, healthy dogs were fed a basal diet supplemented with GA (0%, 0.02%, 0.04%, and 0.08%) for 45 d, and fecal microbiota and metabolomics were evaluated. This study demonstrated that GA supplementation regulated serum lipid metabolism by reducing serum triglyceride, fat digestibility, and Bacteroidetes/Firmicutes ratio. In addition, the relative abundance of Parasutterella was significantly lower, and the SCFAs-producing bacteria were increased along with fecal acetate and total SCFAs contents accumulation in the 0.08% GA group. Metabolomics data further elucidated that 0.08% GA significantly affected carbohydrate metabolism by downregulating succinic acid in fece, thereby alleviating inflammation and oxidative stress. Overall, this study confirmed the beneficial effects of long-term consumption of GA on lipid metabolism and gut health, and the optimal level of GA supplementation was 0.08%., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)

Plant polyphenols have been extensively studied for their chemopreventive properties for human health. Dextransucrase plays an essential role in synthesizing exopolysaccharides from its exclusive substrate sucrose in Streptococcus mutans . In the present study, the effect of polyphenols gallic acid and tannic acid was investigated on the dextransucrase activity. The enzyme was purified by ethanol precipitation followed by column chromatography by Sephadex G-200 gel chromatography, followed by PEG-400 treatment. The purified enzyme exhibited 52 fold enrichment with 17.5% yield and specific activity of 3.54 Units/mg protein. On SDS-PAGE enzyme protein gave a single band with a molecular weight of 160 kDa. Dextransucrase activity was inhibited 80-90% by 0.04 mM tannic acid (TA) or 0.4 mM gallic acid (GA) suggesting that tannic acid has 10- fold more inhibitory potential than gallic acid on the activity of dextransucrase. CD/ORD studies revealed modifications in the tertiary structure of enzyme protein in presence of tannic acid and gallic acid, which were further confirmed by fluorescence spectra of the protein in presence of tannic acid. These results suggest that inhibition of dextransucrase activity in S. mutans by polyphenols may have potential applications in the prevention and control of dental caries., Competing Interests: All authors declare that there is no conflict of interest with the contents of this article., (© 2021 Published by Elsevier B.V.)

Gallic acid (GA) is a known phenolic compound with anti-inflammatory, antioxidant, and anti-cancer activities. The objective of this research is to evaluate the preventive role of GA against carbon tetrachloride (CCl 4 ) induced liver fibrosis. Thirty-five (35) male Wistar rats were used in this study and were equally distributed into five groups (7 rats each). All groups were acclimatized for a week, Group I (control) rats were administered distilled water only. Group II rats were induced with a single dose of CCl 4 (1.25 mL/kg in olive oil (1:1); IP) to cause hepatic damage, while Groups III, IV, and V, rats were intoxicated with CCl 4 . After 24 h the rats in groups III, IV, and V were given 50 mg/kg of silymarin, 50 mg/kg of GA, and 100 mg/kg of GA daily for one week respectively. Rats were sacrificed and fasting blood was estimated for biochemical analysis while the liver was excised for molecular studies. Results from this study revealed that GA significantly decreases serum hepatic enzymes, down-regulate the expression of pro-inflammatory cytokines, interleukin 1 beta (IL-1B), interleukin 6 (IL-6), cyclooxygenase 2 (COX 2), and tumor necrosis factor-alpha (TNF α), and up-regulate antioxidant gene expression (superoxide dismutase and catalase). The use of gallic acid as natural antioxidants can be promising in ameliorating liver diseases., Competing Interests: The authors declare no conflict of interest, (© 2021 The Authors. Published by Elsevier B.V.)

Background: The consumption of green tea catechins (GTCs) suppresses age-related cognitive dysfunction in mice. GTCs are composed of several catechins, of which epigallocatechin gallate (EGCG) is the most abundant, followed by epigallocatechin (EGC). Orally ingested EGCG is hydrolyzed by intestinal biota to EGC and gallic acid (GA). To understand the mechanism of action of GTCs on the brain, their permeability of the blood brain barrier (BBB) as well as their effects on cognitive function in mice and on nerve cell proliferation in vitro were examined., Methods: The BBB permeability of EGCG, EGC and GA was examined using a BBB model kit. SAMP10, a mouse model of brain senescence, was used to test cognitive function in vivo . Human neuroblastoma SH-SY5Y cells were used to test nerve cell proliferation and differentiation., Results: The in vitro BBB permeability (%, in 30 min) of EGCG, EGC and GA was 2.8±0.1, 3.4±0.3 and 6.5±0.6, respectively. The permeability of EGCG into the BBB indicates that EGCG reached the brain parenchyma even at a very low concentration. The learning ability of SAMP10 mice that ingested EGCG (20 mg/kg) was significantly higher than of mice that ingested EGC or GA. However, combined ingestion of EGC and GA showed a significant improvement comparable to EGCG. SH-SY5Y cell growth was significantly enhanced by 0.05 µM EGCG, but this effect was reduced at higher concentrations. The effect of EGC and GA was lower than that of EGCG at 0.05 µM. Co-administration of EGC and GA increased neurite length more than EGC or GA alone., Conclusion: Cognitive dysfunction in mice is suppressed after ingesting GTCs when a low concentration of EGCG is incorporated into the brain parenchyma via the BBB. Nerve cell proliferation/differentiation was enhanced by a low concentration of EGCG. Furthermore, the additive effect of EGC and GA suggests that EGCG sustains a preventive effect after the hydrolysis to EGC and GA.

Purpose: In vitro disintegration and dissolution are routine methods used to assess the performance and quality of oral dosage forms. The purpose of the current work was to determine the potential for interaction between capsule shell material and a green tea extract and the impact it can have on the release., Methods: A green tea extract was formulated into simple powder-in-capsule formulations of which the capsule shell material was either of gelatin or HPMC origin. The disintegration times were determined together with the dissolution profiles in compendial and biorelevant media., Results: All formulations disintegrated within 30 min, meeting the USP criteria for botanical formulations. An immediate release dissolution profile was achieved for gelatin capsules in all media but not for the specified HPMC formulations. Dissolution release was especially impaired for HPMCgell at pH 1.2 and for both HPMC formulations in FeSSIF media suggesting the potential for food interactions., Conclusions: The delayed release from studied HPMC capsule materials is likely attributed to an interaction between the catechins, the major constituents of the green tea extract, and the capsule shell material. An assessment of in vitro dissolution is recommended prior to the release of a dietary supplement or clinical trial investigational product to ensure efficacy.