Chemical Constituents and Biological Activities of Piper as Anticancer Agents: A Review.

Cancer has become the primary cause of death worldwide, and anticancer drugs are used to combat this disease. Synthesis of anticancer drugs has limited success due to adverse side effects has made compounds from natural products with minimal toxicity gain much popularity. Piper species are known to have a biological effect on human health. The biological activity is due to Piper species rich with active secondary metabolites that can combat most diseases, including cancer. This review will discuss the phytochemistry of Piper species and their anticancer activity. The identification and characterization of ten active metabolites isolated from Piper species were discussed in detail and their anticancer mechanism. These metabolites were mainly found could inhibit anticancer through caspase and P38/JNK pathways. The findings discussed in this review support the therapeutic potential of Piper species against cancer due to their rich source of active metabolites with demonstrated anticancer activity.

In vitro antiplasmodial and cytotoxicity activities of crude extracts and major compounds from Goniothalamus lanceolatus.

ETHNOPHARMACOLOGICAL RELEVANCE: Malaria, a devastating infectious disease which was initially recognized as episodic fever, is caused by parasitic protozoan of the genus Plasmodium. Medicinal plants with ethnobotanical information to treat fever and/or malaria has been the key element in identifying potential plant candidates for antimalarial screening. Goniothalamus lanceolatus Miq. (Annonaceae) is used as a folk remedy, particularly to treat fever and skin diseases. AIM OF THE STUDY: In this context, supported with previous preliminary data of its antiplasmodial activity, this study was undertaken to determine the in vitro antiplasmodial and cytotoxicity activities of G. lanceolatus crude extracts and its major compounds. MATERIALS AND METHODS: The in vitro antiplasmodial activity was determined by parasite lactate dehydrogenase (pLDH) assay on chloroquine-sensitive (3D7) and chloroquine-resistant (K1) strains of Plasmodium falciparum. The cytotoxicity activity was evaluated using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay on hepatocellular carcinoma (HepG2) and normal liver (WRL-68) cell lines. RESULTS: The root methanol extract possessed potent antiplasmodial activity against both P. falciparum 3D7 and K1 strains (IC50 = 2.7 µg/ml, SI = 140; IC50 = 1.7 µg/ml, SI = 236). Apart from the DCM extract of stem bark and root that were found to be inactive (IC50 > 50 µg/ml) against 3D7 strain, all other tested crude extracts exhibited promising (5< IC50 < 15 µg/ml) to moderate (15< IC50 < 50 µg/ml) antiplasmodial activity against both strain. Additionally, only compound C (Parvistone D) exerted promising antiplasmodial activity against 3D7 strain (IC50 = 7.5 µM, SI = 51) whereas compound A, B and D showed moderate antiplasmodial activity against the same strain (20 < IC50 < 100 µM). Interestingly, when tested on K1 strain, compound A, C and D exhibited promising antiplasmodial activity (2 < IC50 < 20 µM) while compound B exhibited moderate activity (IC50 = 26.9 µM). Cytotoxicity study showed that all tested crude extracts and compounds were non-toxic on WRL-68 and HepG2 cell lines (CC50 > 30 µg/ml, CC50 > 10 µM, respectively), except for the hexane and DCM extracts of root, which exerted mild cytotoxicity on HepG2 cell line (IC50 < 30 µg/ml). CONCLUSIONS: This study suggests that the root methanol extract and compound C (Parvistone D) obtained from G. lanceolatus are highly potential for exploitation as source of antimalarial agents. Parvistone D is identified as one of the bioactive styryl lactones found in the plant extract. It is also noteworthy, that the extract and compound were more active against chloroquine-resistant (K1) strain of P. falciparum. Further studies are being carried out to assess their toxicity profile and antimalarial efficacy in animal model.

Polymer Based Protein Therapeutics.

Proteins have played a very important role in the drug industry for developing treatments of various diseases such as auto-immune diseases, cancer, diabetes, mental disorder, metabolic disease, and others. Therapeutic proteins have high activity and specificity but they have some limitations such as short half-life, poor stability, low solubility and immunogenicity, so they cannot prolong their therapeutic activity. These shortcomings have been rectified by using polymers for the conjugation with proteins. The conjugates of protein-polymer improves the half-lives, stability and makes them non-immunogenic. Poly(ethylene glycol) (PEG), is widely used in the delivery of proteins because it is the current gold standard for stealth polymers in the emerging field of polymer-based delivery as compared to various biodegradable polymers. PEGylation enhances the retention of therapeutic proteins, effectively alters the pharmacokinetics and enhances the pharmaceutical value. Smart polymer have been used to cope with the pathophysiological environment of target site and have imposed less toxic effects.The contents of this article are challenges in formulation of therapeutic proteins, synthetic routes of conjugates, smart polymer-protein conjugates and also some advantages/disadvantages of polymers as a carrier system of proteins.