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Paper: Hepatoprotective effect of Physalis divaricata in paracetamol induced hepatotoxicity: In vitro, in silico and in vivo analysis

Abstract

Ethnopharmacological relevance

Physalis divaricata D. Don. is an erect weed of family Solanaceae. The root extract of this plant is used by the indigenous communities of Sub-Himalayan region of Uttarakhand, India for the treatment of liver disorders.
Aim of the study

To evaluate hepatoprotective potential of P. divaricata in paracetamol (PCM) induced hepatotoxicity in rats.
Materials and methods

The dried roots of P. divaricata were subjected to extraction using different solvents. The chloroform extract, methanol extract and bioactive aqueous fraction of methanol extract were evaluated for hepatoprotective effect. After initial in vitro screening, all extracts were screened for hepatoprotective potential in PCM (3 g/kg p.o) induced hepatotoxicity. Following PCM administration, extracts were administered orally for 7 days in increasing dose concentrations. All the animals were euthanized on eighth day, serum and liver tissues were collected and subjected to various biochemical and histopathological analysis. Aqueous fraction of methanol extract was further analyzed using LC- MS analysis.


Results

Methanol extract and its bioactive aqueous fraction exhibited significant and better in vitro antioxidant and antiproliferative activity as compared to chloroform extract. PCM treatment caused hepatotoxicity as assessed by altered levels of various hepatic biomarkers (increase in the levels of ALT, AST, ALP, albumin, triglycerides, cholesterol, TBARS, and AOPPs as well as decrease in GSH and TrxR levels) along with histopathological changes (portal to portal bridging, necrosis, and inflammation). Methanolic extract (200, 400 and 800 mg/kg) and its aqueous fraction treatment (25, 50 and 100 mg/kg) significantly restored elevated hepatic biomarkers, oxidative stress, and protected normal hepato-architecture. LC-MS analysis of aqueous fraction showed presence of rutin and kaempferol. In silico analysis further showed the capability of rutin to make complex with TNF-α and block its interaction with the target site.
Conclusion

Aqueous fraction showed maximum hepatoprotective potential as conceived through in vitro and in vivo studies. Presence of rutin may explain hepatoprotective potential of P. divaricata.

AuthorsHasandeep Singha
Tanveer Singh
Amrit Pal Singh
Sarabjit Kaur
Saroj Arorac
Balbir Singha
Published onJournal of Ethnopharmacology
Volume 290, 23 May 2022, 115024
Linkhttps://www.sciencedirect.com/science/article/abs/pii/S0378874122000587
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Paper: Proteins in human body fluids contain in vivo antigen analog of the melibiose-derived glycation product: MAGE

AbstractMelibiose-derived AGE (MAGE) is an advanced glycation end-product formed in vitro in anhydrous conditions on proteins and protein-free amino acids during glycation with melibiose. Our previous studies revealed the presence of MAGE antigen in the human body and tissues of several other species, including muscles, fat, extracellular matrix, and blood. MAGE is also antigenic and induces generation of anti-MAGE antibody. The aim of this paper was to identify the proteins modified by MAGE present in human body fluids, such as serum, plasma, and peritoneal fluids. The protein-bound MAGE formed in vivo has been isolated from human blood using affinity chromatography on the resin with an immobilized anti-MAGE monoclonal antibody. Using mass spectrometry and immunochemistry it has been established that MAGE epitope is present on several human blood proteins including serum albumin, IgG, and IgA. In serum of diabetic patients, mainly the albumin and IgG were modified by MAGE, while in healthy subjects IgG and IgA carried this modification, suggesting the novel AGE can impact protein structure, contribute to auto-immunogenicity, and affect function of immunoglobulins. Some proteins in peritoneal fluid from cancer patients modified with MAGE were also observed and it indicates a potential role of MAGE in cancer.
AuthorsKinga Gostomska-Pampuch, Andrzej Gamian, Karol Rawicz-Pruszyński, Katarzyna Gęca, Joanna Tkaczuk-Włach, Ilona Jonik, Kinga Ożga & Magdalena Staniszewska 
Published onScientific Reports volume 12, Article number: 7520 (2022)
Linkhttps://www.nature.com/articles/s41598-022-11638-2
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Paper: Omeprazole prevents stress induced gastric ulcer by direct inhibition of MMP-2/TIMP-3 interactions

Abstract The healing of damaged tissues in gastric tract starts with the extracellular matrix (ECM) remodeling by the action of matrix metalloproteinases (MMPs). Particularly, MMP-2 (gelatinase-A) maintains ECM structure and function by degrading type IV collagen, the major component of basement membranes and by clearing denatured collagen. The proteolytic activities of MMPs are critically balanced by endogenous tissue inhibitors of metalloproteinases (TIMPs) and disruption of this balance results in several diseases. The well-known drug omeprazole is a proton pump inhibitor used for curing gastric ulcer. However, the action of omeprazole in ECM remodeling on gastroprotection has never been explored. Herein, using rat model of gastric ulcer, we report that restraint cold stress caused increase apoptosis to surface epithelia of gastric tissues along with TIMP-3 upregulation and inhibition of MMP-2 activity thereon. In contrast, omeprazole treatment suppressed TIMP-3 while increasing MMP-2 activity and thereby, restoring MMP-2/TIMP-3 balance. Additionally, nanomolar binding constant (Kd = 318 nM) of omeprazole with purified MMP-2 indicates a direct effect of omeprazole in restoring MMP-2 activity. Further in silico simulations revealed a plausible mechanism of action of omeprazole for TIMP-3 deactivation. Altogether, omeprazole restores MMP-2 activity and reduces apoptosis while preventing acute stress-induced gastric ulcer that occurs via suppression of nuclear factor kappa B (NF-κB) activity and peroxisome proliferator-activated receptor gamma activity (PPAR-γ). This represents an unprecedented correlation between physical docking of drug molecule to a protease and the severity of organ injury and provides a novel therapeutic approach to prevent stress induced tissue damage.
Authors Deep Sankar Rudra
Uttam Pal
Nilkanta Chowdhury
Nakul Chandra Maiti
Angshuman Bagchi
Snehasikta Swarnakara
Published on Free Radical Biology and Medicine
Volume 181, March 2022, Pages 221-234
Link https://www.sciencedirect.com/science/article/abs/pii/S0891584922000600
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Paper: Human Coxsackie- and adenovirus receptor is a putative target of neutrophil elastase-mediated shedding

AbstractDuring viral-induced myocarditis, immune cells migrate towards the site of infection and secrete proteases, which in turn can act as sheddases by cleaving extracellular domains of transmembrane proteins. We were interested in the shedding of the Coxsackie- and adenovirus receptor (CAR) that acts as an entry receptor for both eponymous viruses, which cause myocarditis. CAR shedding by secreted immune proteases could result in a favourable outcome of myocarditis as CAR’s extracellular domain would be removed from the cardiomyocytes’ surface leading to decreased susceptibility to ongoing viral infections.
AuthorsLeonie Herrmann, Louise Schelletter, Raimund Hoffrogge, Karsten Niehaus, Volker Rudolph & Martin Farr
Published onMolecular Biology Reports volume 49, pages 3213–3223 (2022)
Linkhttps://link.springer.com/article/10.1007/s11033-022-07153-2
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