In the present study we investigated the hepatotoprotective, hepatitis B virus (HBV) inhibitory and hepatic CYP450 enzyme (CYP3A4) modulatory potential of Cyperus rotundus rhizome fractions. The crude ethanol-extract, including different organic and aqueous fractions were tested for in vitro cytoprotection on HepG2 cells (MTT assay), followed by in vivo evaluation in Wistar rats (serum biochemistry and lipid profile). The in vitro anti-HBV activity was tested on HepG2.2.15 cells (HBsAg and HBeAg Elisa). Of these, the n-butanol and aqueous fractions showed the most promising, dose-dependent hepatoprotection in DCFH-injured HepG2 cells. Further, in CCl 4 -injured rats, oral administration of C. rotundus (100 and 200 mg/kg·bw/day) significantly normalized serum markers of healthy liver function (SGOT, SGPT, GGT, ALP and bilirubin) and lipid profile (cholesterol, HDL, LDL, VLDL, TG and MDA), including tissue NP-SH and TP levels. Compared to other fractions, the ethyl acetate, n-butanol and aqueous fractions exhibited the best inhibitory effects on viral HBsAg and HBeAg secretions in dose- and time-dependent manner. In addition, reporter gene assay (Dual-luciferase) of transfected HepG2 cells showed mild activation of nuclear PXR-mediated CYP3A4 gene by the three active fractions. Taken together, C. rotundus showed very promising hepatoprotective and anti-HBV potential in experimental settings . In addition, this is the first report on modulation of CYP3A4 by C. rotundus that suggests its safe consumption in relation to drug metabolism and efficacy. Our data could therefore, provide the basis for the ethnobotanical medicinal use of C. rotundus in metabolic liver disorder and hepatitis B patients.

The gastrointestinal tract is colonized by trillions of bacteria and, any injury of the gut barrier causes their translocation to liver and pathogenesis, directly or indirectly. The bacterial infections manifest as liver abscess, acute hepatitis, granulomatous hepatitis, hepatic tuberculosis, spontaneous peritonitis, spontaneous empyema, syphilitic hepatitis, and hepatic brucellosis. The diagnosis includes standard assays for stool and blood culture, biochemistry of liver function and radiology. Chemotherapy with antibiotics as per international guidelines is the treatment option.

In recent times, nanomedicine has effectively addressed the poor delivery, solubility, absorption or cytotoxicity issues of conventional and herbal drugs. Several herbals or bioactive metabolites because of their ability to efficiently reduce and stabilize metal ions have been exploited as herb-synthesized gold and silver nanoparticles. Outbreaks of pathogenic viruses cause significant morbidity and mortality, worldwide. Of these, the novel SARS-Coronavirus-2 disease (COVID-19) remains the most devastating pandemic ever. In view of this, herbal gold and silver nanoparticles have been developed as antiviral drug-delivery carriers against Human immunodeficiency virus, Herpes virus, Influenza virus, Dengue virus, Chikungunya virus and Hepatitis B virus etc. Notable examples include Astragalus membranaceus, Tinospora cordifolia, Phyllanthus niruri, Andrographis paniculate, Lampranthus coccineus and Malephora lutea synthesized antiviral nanoparticles. Although further studies have shown that such herbal-synthesized nanoparticles could enter the target cells and inhibit virus replication, their interactions with different cell types and the specific mechanism of antiviral activities still remain inconclusive.