System Biology Investigation Revealed Lipopolysaccharide and Alcohol-Induced Hepatocellular Carcinoma Resembled Hepatitis B Virus Immunobiology and Pathogenesis.

Hepatitis B infection caused by the hepatitis B virus is a life-threatening cause of liver fibrosis, cirrhosis, and hepatocellular carcinoma. Researchers have produced multiple in vivo models for hepatitis B virus (HBV) and, currently, there are no specific laboratory animal models available to study HBV pathogenesis or immune response; nonetheless, their limitations prevent them from being used to study HBV pathogenesis, immune response, or therapeutic methods because HBV can only infect humans and chimpanzees. The current study is the first of its kind to identify a suitable chemically induced liver cirrhosis/HCC model that parallels HBV pathophysiology. Initially, data from the peer-reviewed literature and the GeneCards database were compiled to identify the genes that HBV and seven drugs (acetaminophen, isoniazid, alcohol, D-galactosamine, lipopolysaccharide, thioacetamide, and rifampicin) regulate. Functional enrichment analysis was performed in the STRING server. The network HBV/Chemical, genes, and pathways were constructed by Cytoscape 3.6.1. About 1546 genes were modulated by HBV, of which 25.2% and 17.6% of the genes were common for alcohol and lipopolysaccharide-induced hepatitis. In accordance with the enrichment analysis, HBV activates the signaling pathways for apoptosis, cell cycle, PI3K-Akt, TNF, JAK-STAT, MAPK, chemokines, NF-kappa B, and TGF-beta. In addition, alcohol and lipopolysaccharide significantly activated these pathways more than other chemicals, with higher gene counts and lower FDR scores. In conclusion, alcohol-induced hepatitis could be a suitable model to study chronic HBV infection and lipopolysaccharide-induced hepatitis for an acute inflammatory response to HBV.

Ethyl gallate isolated from phenol-enriched fraction of Caesalpinia mimosoides Lam. Promotes cutaneous wound healing: a scientific validation through bioassay-guided fractionation.

The tender shoots of Caesalpinia mimosoides Lam. are used ethnomedically by the traditional healers of Uttara Kannada district, Karnataka (India) for the treatment of wounds. The current study was aimed at exploring phenol-enriched fraction (PEF) of crude ethanol extract of tender shoots to isolate and characterize the most active bio-constituent through bioassay-guided fractionation procedure. The successive fractionation and sub-fractionation of PEF, followed by in vitro scratch wound, antimicrobial, and antioxidant activities, yielded a highly active natural antioxidant compound ethyl gallate (EG). In vitro wound healing potentiality of EG was evidenced by a significantly higher percentage of cell migration in L929 fibroblast cells (97.98 ± 0.46% at 3.81 µg/ml concentration) compared to a positive control group (98.44 ± 0.36%) at the 48th hour of incubation. A significantly higher rate of wound contraction (98.72 ± 0.41%), an elevated tensile strength of the incised wound (1,154.60 ± 1.42 g/mm2), and increased quantity of connective tissue elements were observed in the granulation tissues of the 1% EG ointment treated animal group on the 15th post-wounding day. The accelerated wound healing activity of 1% EG was also exhibited by histopathological examinations through Hematoxylin and Eosin, Masson's trichome, and Toluidine blue-stained sections. Significant up-regulation of enzymatic and non-enzymatic antioxidant contents (reduced glutathione, superoxide dismutase, and catalase) and down-regulation of oxidative stress marker (lipid peroxidation) clearly indicates the effective granular antioxidant activity of 1% EG in preventing oxidative damage to the skin tissues. Further, in vitro antimicrobial and antioxidant activities of EG supports the positive correlation with its enhanced wound-healing activity. Moreover, molecular docking and dynamics for 100 ns revealed the stable binding of EG with cyclooxygenase-2 (-6.2 kcal/mol) and matrix metalloproteinase-9 (-4.6 kcal/mol) and unstable binding with tumor necrosis factor-α (-7.2 kcal/mol), suggesting the potential applicability of EG in inflammation and wound treatment.

In Silico Study on the Interactions, Molecular Docking, Dynamics and Simulation of Potential Compounds from Withania somnifera (L.) Dunal Root against Cancer by Targeting KAT6A.

Cancer is characterized by the abnormal development of cells that divide in an uncontrolled manner and further take over the body and destroy the normal cells of the body. Although several therapies are practiced, the demand and need for new therapeutic agents are ever-increasing because of issues with the safety, efficacy and efficiency of old drugs. Several plant-based therapeutics are being used for treatment, either as conjugates with existing drugs or as standalone formulations. Withania somnifera (L.) Dunal is a highly studied medicinal plant which is known to possess immunomodulatory activity as well as anticancer properties. The pivotal role of KAT6A in major cellular pathways and its oncogenic nature make it an important target in cancer treatment. Based on the literature and curated datasets, twenty-six compounds from the root of W. somnifera and a standard inhibitor were docked with the target KAT6A using Autodock vina. The compounds and the inhibitor complexes were subjected to molecular dynamics simulation (50 ns) using Desmond to understand the stability and interactions. The top compounds (based on the docking score of less than -8.5 kcal/mol) were evaluated in comparison to the inhibitor. Based on interactions at ARG655, LEU686, GLN760, ARG660, LEU689 and LYS763 amino acids with the inhibitor WM-8014, the compounds from W. somnifera were evaluated. Withanolide D, Withasomniferol C, Withanolide E, 27-Hydroxywithanone, Withanolide G, Withasomniferol B and Sitoindoside IX showed high stability with the residues of interest. The cell viability of human breast cancer MCF-7 cells was evaluated by treating them with W. Somnifera root extract using an MTT assay, which showed inhibitory activity with an IC50 value of 45 µg/mL. The data from the study support the traditional practice of W. somnifera as an anticancer herb.

A validated spectro densitometric regulatory compliant USP-HP-TLC protocol for quantification of polyphenols and antioxidants from polyherbal formulations containing Terminalia species.

The phytochemical profiles of ethno-medicinal plants from Southern Asia have been extensively studied, due to their wide utilization in various traditional systems of India, Bhutan, Maldives, Nepal and China. Terminalia bellirica (Gaertn.) Roxb. and Terminalia chebula Retz. are the two most important and widely utilized medicinal plants across the traditional system in India. The herbal products comprising the fruits of these two plants, example Triphala, Vyoshadi-Gulgulu Gulika and also marketed Ayurvedic products like Pilonil Tablet are proven to have high medicinal value and biotherapeutic efficacy. The current study is an effort to develop highly precise, sensitive and reproducible HP-TLC protocol for the standardization herbal preparations comprising of hydro-alcoholic extract of selected Terminalia species as their major ingredients. The selected herbal products were assessed through HP-TLC for quantifying gallic acid and quercetin, followed by their visualization using DPPH*, Anisaldehyde and Vanillin as derivatizing reagent. The USP official protocol was followed for the method development using digitally optimized HP-TLC system. The results demonstrated good sensitivity and regression value of 99.999% for proposed method with optimized chromatographic analysis. The developed protocol was validated in accordance with ICH guidelines and all the parameters were found to be within the specified limits. Thus, the proposed HP-TLC method would surely serve as a classical tool for analysis and standardization of Terminalia species and their traditional products.

Total polyphenolic contents and in vitro antioxidant properties of eight Sida species from Western Ghats, India.

BACKGROUND: Sida L., is a medicinally important genus, the species of which are widely used in traditional systems of medicine in India. Pharmacologically, roots are known for anti-tumor, anti-HIV, hepatoprotective, and many other properties. Phenolic antioxidants help in reducing oxidative stress occurring during treatment of such diseases. OBJECTIVE: The study aimed to evaluate and compare polyphenol contents and antioxidant properties of eight selected species of Sida from Western Ghats, India. MATERIALS AND METHODS: Methanolic root extracts (10% w/v) of Sida species, viz., S. acuta, S. cordata, S. cordifolia, S. indica, S. mysorensis, S. retusa, S. rhombifolia, and S. spinosa were analyzed. RESULTS: Sida cordifolia possessed highest total phenolic content (TPC: 1.92 ± 0.10 mg Caffeic Acid Equivalent/g and 2.13 ± 0.11 mg Tannic Acid Equivalant/g), total flavonoid content (TF: 2.60 ± 0.13 mg Quercetin Equivalent/g) and also possessed highest antioxidant activities in 2,2-diphenylpicrylhydrazyl (DPPH) radical scavenging (51.31 ± 2.57% Radical Scavenging Activity, (RSA); Trolox Equivalent Antioxidant Capacity: 566.25 ± 28.31µM; Ascorbic acid Equivalent Antioxidant Capacity: 477.80 ± 23.89 µM) and Ferric Reducing Antioxidant Power assays (TEAC: 590.67 ± 29.53 µM; AEAC: 600.67 ± 30.03 µM). Unlike DPPH and Ferric Reducing Antioxidant Power (FRAP) activity, 2, 2'-Azinobis (3-ethyl Benzo Thiazoline-6-Sulfonic acid) ABTS(+) antioxidant activity was highest in S. indica (TEAC: 878.44 ± 43.92 µM; AEAC 968.44 ± 48.42 µM). It was significant to note that values of AEAC (µM) for all the antioxidant activities analyzed were higher than that of TEAC. CONCLUSION: The high contents of phenolic compounds in the root extracts of selected Sida species have direct correlation with their antioxidant properties. Conclusively, roots of S. cordifolia can be considered as the potential source of polyphenols and antioxidants.

Evaluating Nothapodytes nimmoniana population from three localities of Western Ghats using camptothecin as phytochemical marker and selection of elites using a new-content range chart method.

BACKGROUND: Nothapodytes nimmoniana (Grah.) Mabb. is a high valued medicinal plant endemic to Western Ghats of India, distributed in fragmented populations. The plant is valued for potent anticancer drug camptothecin (CPT). OBJECTIVE: The study compares and expounds variation in CPT content from leaves and stems of N. nimmoniana obtained from three populations of Western Ghats, India. The study also describes a method for categorizing these populations using content range chart (CRC) method for percent yield of CPT. MATERIALS AND METHODS: A total of 60 samples were investigated including ten each of leaves and stems from three localities. Micro-extraction method was implemented to extract CPT. reversed phase ultra-performance liquid chromatography photo diode array technique was used to quantify CPT. RESULTS: Leaf samples of an individual collected from Joida, yielded lowest CPT content (0.002 ± 0.000 g/100 g), whereas a stem sample from Amgaon, yielded highest CPT content (0.123 ± 0.006 g/100 g). The findings suggest great variation in individuals producing and accumulating CPT. Using this data along with earlier published work, five categories of CPT yielding plants were made viz. I: Very low: <0.020, II: Low: 0.021-0.039, III: Moderate: 0.040-0.059, IV: High: 0.060-0.079 and V: Very high: >0.080. Based on CPT content in leaves, majority of individuals were under very low category (I(st)) and on the other hand stem samples were in 'II' category. Besides, very few individuals were observed in category 'V'. CONCLUSION: The study expounds use of CRC method for identifying elite population and suggests the need for its conservation.

Comparative toxicity profiles of Plumbago zeylanica L. root petroleum ether, acetone and hydroalcoholic extracts in Wistar rats.

INTRODUCTION: The root of Plumbago zeylanica Linn. is used in traditional medicine for the treatment of chronic inflammatory diseases and various disorders. The toxicity of this plant has not yet been extensively evaluated. AIM: To evaluate and compare the toxicity of P. zeylanica root petroleum ether (PZPE), acetone (PZAC), and the hydroalcoholic (PZHY) extracts. MATERIALS AND METHODS: The acute and sub-acute toxicities of extracts were evaluated according to OECD guidelines 425 and 407, respectively in female rats. RESULTS: PZPE was more toxic than PZAC and PZHA, based on LD50 values of 93.45, 928.4, and 928.4 mg/kg, respectively. This potency difference directly correlates with the plumbagin content of extracts. With regard to sub-acute toxicity, a significant increase in organ weights (liver, adrenal glands, and/or heart) was observed in PZPE and PZAC treated groups. All extracts produced a significant increase in serum aspartate aminotransferase and urea, and PZAC produced a significant increase in serum creatinine as compared to control. A decrease in hematocrit was observed in the highest dose PZPE group, and a decrease in leukocytes was observed in all PZAC groups. Hepatic and renal changes were observed in all extract treated groups. CONCLUSION: The findings of our study, thus demonstrate that liver and kidney are the primary organs being adversely affected following sub-acute administration of P. zeylanica root extract in rats.