Abstract
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.
Similar content being viewed by others
Abbreviations
- ADAMTS:
-
disintegrin containing metalloproteinases with thrombospondin motifs
- HA:
-
hyaluronic acid
- HPTLC:
-
high-performance thin layer chromatography
- MMP:
-
matrix metalloproteinase
- OA:
-
osteoarthritis
- TG:
-
Triphala guggulu
- TSG:
-
Triphala shodith guggulu
References
Abraham S, Kumar M S, Sehgal P K, Nitish S and Jayakumar N D 2005 Evaluation of the inhibitory effect of triphala on PMN-type matrix metalloproteinase (MMP-9); J. Periodontol. 76 497–502
Arora R B, Kapoor V, Gupta S K and Sharma R C 1971 Isolation of a crystalline steroidal compound from Commiphora mukul and its anti-inflammatory activity; Indian J. Exp. Biol. 9 403–404
Banerjee P 2002 Quality control of herbal drugs (New Delhi: Business Horizons) pp 723–725
Chunekar K C and Pandeya G S 1995 Bhavaprakashnighantu 10th edition (Varanasi: Chaukhabha Bharati Academy) p. 206
Demeule M, Brossard M, Page M et al 2000 Matrix metalloproteinase inhibition by green tea catechins; Biochem. Biophys. Acta 1478 51–60
Girish K S and Kemparaju K 2005 Inhibition of Naja naja venom hyaluronidase by plant derived bioactive components and polysaccharides; Biochemistry (Mosc) 70 948–952
Evans C H 1991 The role of proteinases in cartilage destruction; Agents Actions Suppl. 32 135–152
Harsulkar A M, Giri A P, Gupta V S, Sainani M N, Deshpande V V, Patankar A G and Ranjekar P K 1998 Characterization of Helicoverpa armigera gut proteinases and their interaction with proteinase inhibitors using gel X-ray film contact print technique; Electrophoresis 19 1397–1402
Indian herbal Pharmacopeia Revised edn. 2002 (Mumbai: Indian Drug Manufacturers Association) pp 493–496
Jagetia G S, Rao S K, Baliga M S and Babu K 2004 The evaluation of nitric oxide scavenging activity of certain herbal formulations in vitro: a preliminary study; Phytother. Res. 18 561–565
Marquina M A, Coroa G M, Araujo L, Buitrago D and Sosa M 2002 Hyaluronidase inhibitory activity from the polyphenols in the fruit of blackberry (Rubus fruticosus B); Fitoterapia 73 727–729
Murphy G and Lee M H 2005 What are the roles of matrixmetalloproteinases in cartilage and bone repair?; Ann. Rheum. Dis. 64 44–47
Pavelka K, Forejtova S and Olejarova M 2004 Hyaluronic acid levels may have predictive value for the progression of knee osteoarthritis; Osteoarthritis Cartilage 21 277–278
Porter S, Clark I M, Kevorkian L and Edwards D R 2005 The ADAMTS metalloproteinases; Biochem J. 386 15–27
Pelletier J P and Martel-Pelletier J 1993 Effects of nimesulide and naproxen on the degradation and metalloprotease synthesis of human osteoarthritic cartilage; Drugs (Suppl. 1) 46 134–139
Shaha N C 1985 The encyclopedia of ayurvedic formulations (New Delhi: B Jain Publishers) Vol 2, pp 360–361
Singh B B, Mishra L C, Vinjamury S P, Aquilina N, Singh V J and Shepard N 2003 The effectiveness of Commiphora mukul for osteoarthritis of the knee: an outcomes study; Altern. Ther. Health Med. 9 74–79
Smith G N Jr, Yu L P Jr, Brandt K D and Capello W N 1998 Oral administration of doxycycline reduces collagenase and gelatinase activities in extracts of human osteoarthritic cartilage; J. Rheumatol. 25 532–535
Stenman M, Ainola M, Valmu L, Bjartell A, Guofeng M, Stenman U-H et al 2005 Trypsin-2 degrades type 2 collagen and is expressed and activated in mesenchymally transformed rheumatoid arthritis synovitis tissue; Am. J. Pathol. 167 1119–1124.
Sumantran V N, Kulkarni A, Boddul S, Chinchwade T, Harsulkar A, Patwardhan B, Chopra A and Wagh U V 2007 Chondroprotective potential of root extracts of Withania somnifera in osteoarthritis; J. Biosci. 32 299–307
Svoboda R E 1992 Ayurvedic life health and longevity 1st edition (New Delhi: Penguin Books) p 221, 258–25
Tanaka N, Sakahashi H, Sato F, Hirose K, Ishima T and Ishi S 2002 Intra-articular injection of high molecular weight hyaluronan after arthrocentesis as treatment for rheumatoid knees with joint effusion; Rheumatol. Int. 4 151–154
Tung J S, Mark G E and Hollis G F 1994 A microplate assay for hyaluronidase and hyaluronidase inhibitors; Anal. Biochem. 223 149–152
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Sumantran, V.N., Kulkarni, A.A., Harsulkar, A. et al. Hyaluronidase and collagenase inhibitory activities of the herbal formulation Triphala guggulu . J Biosci 32, 755–761 (2007). https://doi.org/10.1007/s12038-007-0075-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12038-007-0075-3