Glycosmis pentaphylla is used by traditional people of India against liver disorders from time immemorial. G. pentaphylla   harbours many structurally and functionally diverse chemical entities. We have   isolated   and   characterized a   novel   anti Hepatocellular carcinoma  compound from G. pentaphylla and the elucidation of the molecular mechanism behind their activity using HCC cell lines .The cytotoxicity and apoptosis inducing effect of the active extract and its fractions were evaluated on Hep3 B, HepG2, HEK 293, LX2 and RAW 264.7 cell lines by MTT assay, morphological studies, Hoechst staining, DNA fragmentation assay, reverse transcription polymerase chain reaction and Western blotting.  The  phytochemical  profiling of the active extract was accomplished by different biochemical assays. Compound purification and identification were done using column Chromatography and   different   Spectroscopic  methods. Our studies showed that the alcohol extract of G. pentaphylla contains a compound with the molecular formula C16H16NO4, which is responsible for its selective anti-HCC activity.  Structure activity analysis with in silico methods showed that the isolated compound is a druggable candidate. Comparative docking study of the compound with   Sorafenib  showed a comparable binding   efficacy of the compound on B Raf and mutated B Raf proteins. In vivo acute toxicity   studies demonstrated that the LD₅₀ of both   active   extract and the compound  were above 2g/kg with 0% mortality observed.

Inflammation is a complex pathophysiological process mediated by a variety of signaling molecules produced by leukocytes, macrophages and mast cells undergoing various cellular responses. Tinospora cordifolia (Willd.) Miers is a perennial climbing plant belongs to the famly Menispermaceae. It has been traditionally used for the treatment of fever, arthritis, gout, psoriasis and asthma by different tribal groups of India. The detailed investigations of pharmacological activity  led molecular mechanisms ,we aimed to validate and  mechanistically understand the anti-inflammatory potential of T. cordiflia. Among the different extracts screened, the chloroform extract of T. cordifolia (CETC) exhibited selective COX-2 inhibition property. Hence CETC was selected for doing further in vitro (LPS stimulated RAW264.7 and THP-1 macrophages) as well as in vivo analyses Carrageenan induced acute inflammation and Septic shock model in wistar rats.

Hepatocellular carcinoma (HCC), the most frequent type of primary liver cancer, is the second most common cause of cancer related deaths worldwide. Late diagnosis often leaves the patient with systemic chemotherapy as the sole option for prolonging survival. Herein, glycopentalone, a chalcone isolated and characterized in our lab from the alcohol extract of Glycosmis pentaphylla has been investigated for its molecular basis of action as well as its optimisation using nanocarrier systems.
Mechanistically, glycopentalone induces apoptosis, as evident in HepG2 cells through analysis of different morphological and biochemical hallmarks of apoptosis. Chromatin condensation was visible by Hoechst 33322 staining, externalisation of phosphatidyl serine was observed with FITC conjugated Annexin V, DNA fragmentation was confirmed by laddering on EB stained gel and FACS, and caspase activation was demonstrated through PARP cleavage. Concurrently, autophagy induction was analysed suggesting the activation of pro-survival autophagy. Changes in expression of p62 and co-treatment studies with Bafilomycin A1 proved that autophagy activation is indeed caused by glycopentalone exposure. Further, comparative label free LC-MS/MS analysis elucidated the differential protein expression profile in HepG2 cells upon treatment with glycopentalone and the FDA-approved drug, Sorafenib.

Sorafenib is the only FDA approved agent against unresectable hepatocellular carcinoma (HCC). Unfortunately, its use is limited by undesirable characteristics like poor aqueous solubility and systemic toxicity resulting in decreased bioavailability.. Nanoparticulate technology is one among the several approaches explored to eliminate the concerns associated with hydrophobic phytochemicals thereby enhancing their therapeutic effect on HCC. Nano enabled delivery vehicles for sorafenib and glycopentalone were generated with the hypothesis that incorporation of glycopentalone in nanoparticles would increase its solubility and stability, and thus expand its therapeutic index in HCC. Sorafenib nanoparticles were synthesised for comparison as well as optimisation. In the current study, the delivery systems were based on SPIONs and PLGA. Sorafenib and glycopentalone loaded PVA coated SPIONs as well as glycopentalone loaded PLGA nanoparticles were synthesized individually. The physicochemical characterizations of the synthesized nanoparticles were done using TEM, DSC analysis, XRD, FTIR, Raman spectra and VSM measurements. The adsorption of PVA to the SPIONs and the conjugation of drugs to the nanocarrier were confirmed by XRD, FTIR and Raman spectra analyses. VSM study ascertained the superparamagnetic nature of the drug loaded SPIONs. Cellular uptake studies suggested their efficient entrapment in HepG2 cells. MTT anti-proliferative assay threw light towards the cytotoxicity of both nano formulations, which was comparable or higher than free drug. Dual AO/EB staining, Annexin V/FITC FACS assay, and LC3 immunofluorescence evidenced the activation of apoptosis pathway for the killing of HCC cells by the nanformulation. The safety of the drug conjugated nanoparticles was verified in Wistar rats by acute toxicity testing. This study expects to unravel the molecular events happening in the cells when exposed to glycopentalone in addition to polishing it as a better and safe chemotherapeutic compound against Hepatocellular carcinoma.