Hyaluronidase and collagenase inhibitory activities of the herbal formulation Triphala guggulu.

Myrrh (guggulu) oleoresin from the Commiphora mukul tree is an important component of antiarthritic drugs in Ayurvedic medicine. Clinical data suggest that elevated levels of hyaluronidase and collagenase type 2 enzymes contribute significantly to cartilage degradation. Triphala guggulu (TG) is a guggulu-based formulation used for the treatment of arthritis. We assessed the chondroprotective potential of TG by examining its effects on the activities of pure hyaluronidase and collagenase type 2 enzymes. Triphala shodith guggulu (TSG), an intermediate in the production of TG, was also examined. A spectrophotometric method was used to assay Hyaluronidase activity, and to detect potential Hyaluronidase inhibitors. Aqueous and hydro-alcoholic extracts of TSG showed weak but dose-dependent inhibition of hyaluronidase activity. In contrast, the TG formulation was 50 times more potent than the TSG extract with respect to hyaluronidase inhibitory activity. A validated X-ray film-based assay was used to measure the gelatinase activity of pure collagenase type 2. Hydro-alcoholic extracts of the TG formulation were 4 times more potent than TSG with respect to collagenase inhibitory activity. Components of Triphala were also evaluated for their inhibitory activities on hyaluronidase and collagenase. This is the first report to show that the T2 component of Triphala (T.chebula) is a highly potent hyaluronidase and collagenase inhibitor. Thus, the TG formulation inhibits two major enzymes that can degrade cartilage matrix. Our study provides the first in vitro preclinical evidence of the chondroprotective properties of TG.

Collagenase-IV in human trophoblast invasion and differentiation.

Trophoblast cells are unique with respect to their functions and responsibilities. These cells demonstrate three sequential phenotypes, proliferation and invasion into the endometrium, differentiation to form syncytia and endocrine secretions. Equipped with these properties placental trophoblasts are endowed with a variety of functions, like implantation of the blastocyst to the endometrium, providing nutrition to the developing embryo and also transmitting extraordinary array of signals for the embryonic development. Experimental evidences and logical extrapolation suggest that these functions are precisely controlled by growth factors, cytokines and hormones produced either by the trophoblast themselves or by the utero-placental unit. Any error in this control mechanism has extremely adverse consequences. The cells also synthesize a large number of enzymes, amongst which collagenase type IV secretion is involved in digestion of underlying basement membrane necessary for the process of invasion. Our results implicate the enzyme in the functional differentiation of the trophoblast as well. Inhibitors to this enzyme inhibit trophoblast differentiation as monitored by secretion of hCG and progesterone, the two markers of trophoblastic differentiation. In contrast, BeWo cells, a choriocarcinoma cell line which does not differentiate spontaneously, undergo increased proliferation when challenged with EGF. The results indicate the possibility of invasive and differentiative phenotypes to be coupled. Exact molecular involvements in this coupling process are looked into.