Maninder Karan

Drug-delivery systems employing phytopharmaceuticals based on the leads in traditional knowledge offers not only an alternative but quicker and more economic strategy for drug development. Nanophytopharmaceuticals promise remarkable opportunities with the ability to overcome challenges associated with herbal medicines, such as low solubility and bioavailability, poor target specificity, and shelf life. Berberis extracts documented as Ropana (wound healer) in Sushruta Samhita are a popular traditional remedy that is amiss in the modern system of medicine as it exhibits very poor biopharmaceutical properties. Poor solubility and bioavailability necessitate the administration of high doses to achieve the desired therapeutic effects. Exploiting the diversified type of compounds with pleiotropic properties present in Berberis, the biopharmaceutical properties were engineered using an optimized freeze-dried extract and developed solid lipid nanoparticles (SLNs) as an effective drug-delivery system. An industrially viable and environment-friendly hot high-pressure homogenization technique led to a stable formulation with an average particle size of 178.4 nm, as well as a 7-fold increase in loading and a significant entrapment of 91 ± 1.25%. The pharmacodynamic studies of developed nanosystems in excision-wound models showed faster and complete healing of wounds with no scars.

Gallic acid and its derivatives are potential therapeutic agents for treating various oxidative stress mediated disorders. In the present study, we investigated the hepatoprotective effects of newly synthesized conjugated trimethylgallic acid (TMGA) esters against carbon tetrachloride (CCl4)-induced hepatotoxicity in rats. Animals were pre-treated with TMGA esters at their respective doses for 7 days against CCl4-induced hepatotoxicity. The histopathological changes were evaluated to find out degenerative fatty changes including vacuole formation, inflammation and tissue necrosis. Various biomarkers of oxidative stress (lipid peroxidation, glutathione levels, and endogenous antioxidant enzyme activities), liver enzymes (AST and ALT), triacylglycerol and cholesterol were evaluated. Pre-treatment with TMGA esters (MRG, MGG, MSG, and MUG at the dose of 28.71, 30.03, 31.35, 33.62 mg/kg/day), respectively reversed the CCl4-induced liver injury scores (reduced vacuole formation, inflammation and necrosis), biochemical parameters of plasma (increased AST, ALT, TG, and cholesterol), antioxidant enzymes (increased lipid peroxidation and nitrite levels; decreased glutathione levels, superoxide dismutase and catalase activities) in liver tissues and inflammatory surge (serum TNF-α) significantly. The study revealed that TMGA esters exerted hepatoprotective effects in CCl4-induced rats, specifically by modulating oxidative-nitrosative stress and inflammation.

Many studies have shown that the levels of oxidative stress (increased lipid peroxidation, decreased glutathione levels and endogenous antioxidant enzyme activities) and proinflammatory cytokines (e.g., TNF-α) are increased in patients with chronic fatigue syndrome. Gallic acid and other phenolic compounds are potent antioxidants and inhibitor of cytokine production. The present study was designed to investigate the effect of newly synthesized conjugated esters of trimethylgallic acid in an experimental model of chronic stress. The animals were forced to swim individually for a period of 6min every day for 15 days to induce chronic stress. The locomotor activity, anxiety-like behavior, and memory retention were evaluated in chronically stressed animals, followed by biochemical estimations and neuroinflammatory surge in the brain. Chronic treatment with trimethylgallic acid esters for 15 days significantly reversed the chronic stress-induced behavioral (impaired locomotor activity, anxiety-like behavior, and decreased percentage of memory retention), biochemical (increased lipid peroxidation and nitrite levels; decreased glutathione levels, superoxide dismutase and catalase activities), and inflammation surge (serum TNF-α) in stressed mice. The study revealed that trimethylgallic acid esters could ameliorate chronic stress-induced various behavioral and biochemical alterations in mice, showing protective effects against chronic stress.