ABSTRACT
There is significant number of evidences suggesting the anti-inflammatory properties of gum resin extracts of Boswellia serrata containing 3-O-acetyl-11-keto-ß-boswellic acid (AKBA) and their promising potential as therapeutic interventions against inflammatory diseases such as osteoarthritis (OA). Unfortunately, the poor bioavailability of AKBA following oral administration might limit the anti-inflammatory efficacy of standardized Boswellia extract(s). To address this issue, we describe a novel composition called Aflapin, which contains B. serrata extract enriched in AKBA and non-volatile oil portion of B. serrata gum resin. Our observations show that the availability of AKBA in systemic circulation of experimental animals is increased by 51.78% in Aflapin-supplemented animals, in comparison with that of 30% AKBA standardized extract or BE-30 (5-Loxin(®)). Consistently, Aflapin confers better anti-inflammatory efficacy in Freund's Complete Adjuvant (FCA)-induced inflammation model of Sprague-Dawley rats. Interestingly, in comparison with BE-30, Aflapin(®) also provides significantly better protection from IL-1ß-induced death of human primary chondrocytes and improves glycosaminoglycans production in human chondrocytes. In Tumor necrosis factor alpha (TNFα)-induced human synovial cells, the inhibitory potential of Aflapin (IC(50) 44.736 ng/ml) on matrix metalloproteinase-3 (MMP-3) production is 14.83% better than that of BE-30 (IC(50) 52.528 ng/ml). In summary, our observations collectively suggest that both the Boswellia products, BE-30 (5-Loxin(®)) and Aflapin, exhibit powerful anti-inflammatory efficacy and anti-arthritic potential. In particular, in comparison with BE-30, Aflapin provides more potential benefits in recovering articular cartilage damage or protection from proteolytic degradation due to inflammatory insult in arthritis such as osteoarthritis or rheumatoid arthritis.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Boswellia , Lipoxygenase Inhibitors/pharmacology , Osteoarthritis/drug therapy , Phytotherapy , Plant Extracts/pharmacology , Triterpenes/pharmacology , Animals , Anti-Inflammatory Agents, Non-Steroidal/pharmacokinetics , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Arachidonate 5-Lipoxygenase/metabolism , Biological Availability , Cell Culture Techniques , Cell Death , Cell Line, Tumor , Cell Proliferation , Cells, Cultured , Female , Foot/pathology , Freund's Adjuvant , Glycosaminoglycans/metabolism , Hindlimb/pathology , Humans , Inflammation/chemically induced , Inflammation/drug therapy , Interleukin-1beta , Lipoxygenase Inhibitors/pharmacokinetics , Lipoxygenase Inhibitors/therapeutic use , Male , Matrix Metalloproteinase 3/metabolism , Plant Extracts/pharmacokinetics , Plant Extracts/therapeutic use , Rats , Rats, Sprague-Dawley , Rats, Wistar , Triterpenes/pharmacokinetics , Triterpenes/therapeutic use , Tumor Necrosis Factor-alpha/metabolismABSTRACT
Investigation of the methanol extract of Aswagandha (Withania somnifera) roots for bioactive constituents yielded a novel withanolide sulfoxide compound (1) along with a known withanolide dimer ashwagandhanolide (2) with an S-linkage. The structure of compound 1 was established by extensive NMR and MS experiments. Compound 1 was highly selective in inhibiting cyclooxygenase-2 (COX-2) enzyme by 60% at 100 microm with no activity against COX-1 enzyme. The IC(50) values of compound 1 against human gastric (AGS), breast (MCF-7), central nervous system (SF-268) and colon (HCT-116) cancer cell lines were in the range 0.74-3.63 microm. Both S-containing dimeric withanolides, 1 and 2, completely suppressed TNF-induced NF-kappaB activation when tested at 100 microm. The isolation of a withanolide sulfoxide from W. somnifera roots and its ability to inhibit COX-2 enzyme and to suppress human tumor cell proliferation are reported here for the first time. In addition, this is the first report on the abrogation of TNF-induced NF-kappaB activation for compounds 1 and 2.
Subject(s)
Cell Proliferation/drug effects , Cyclooxygenase 1/metabolism , Cyclooxygenase 2/metabolism , NF-kappa B/antagonists & inhibitors , Sulfoxides/pharmacology , Withanolides/pharmacology , Cell Line, Tumor , Ergosterol/analogs & derivatives , Ergosterol/pharmacology , Humans , Molecular Structure , Plant Extracts/pharmacology , Plant Roots/chemistry , Sulfoxides/isolation & purification , Withania/chemistry , Withanolides/isolation & purificationABSTRACT
A new dimeric withanolide, ashwagandhanolide (1), was isolated from the roots of an Ayurvedic medicinal herb, Withania somnifera. A detailed spectroscopic evaluation revealed its identity as a dimer with an unusual thioether linkage. Compound 1 displayed growth inhibition against human gastric (AGS), breast (MCF-7), central nervous system (SF-268), colon (HCT-116), and lung (NCI H460) cancer cell lines, with IC50 values in the range 0.43-1.48 microg/mL. In addition, it inhibited lipid peroxidation and the activity of the enzyme cyclooxygenase-2 in vitro.
Subject(s)
Antineoplastic Agents, Phytogenic/isolation & purification , Cyclooxygenase Inhibitors/isolation & purification , Ergosterol/analogs & derivatives , Plants, Medicinal/chemistry , Withania/chemistry , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/pharmacology , Cyclooxygenase Inhibitors/chemistry , Cyclooxygenase Inhibitors/pharmacology , Drug Screening Assays, Antitumor , Ergosterol/chemistry , Ergosterol/isolation & purification , Ergosterol/pharmacology , Humans , India , Lipid Peroxidation/drug effects , Molecular Structure , Plant Roots/chemistryABSTRACT
Two triterpenoid glycosides have been isolated along with 10 known saponins from Bacopa monnieri. Structures of the compounds have been elucidated as 3-O-[beta-D-glucopyranosyl-(1-->3)-beta-D-glucopyranosyl] jujubogenin (1) and 3-O-[beta-D-glucopyranosyl-(1-->3)-beta-D-glucopyranosyl] pseudojujubogenin (2) by high resolution NMR spectral data and chemical correlations. Further, the chemical compositions of bacosides A and B have been delineated.
