BackgroundTerminalia chebula (Combretaceae) has been widely used in Ayurveda for the treatment of diabetes. In the present investigation, the chloroform extract of T. chebula seed powder was investigated for its antidiabetic activity in streptozotocin-induced diabetic rats using short term and long term study protocols. The efficacy of the extract was also evaluated for protection of renal functions in diabetic rats.MethodsThe blood glucose lowering activity of the chloroform extract was determined in streptozotocin-induced (75 mg/kg, i.p.; dissolved in 0.1 M acetate buffer; pH 4.5) diabetic rats, after oral administration at the doses of 100, 200 and 300 mg/kg in short term study. Blood samples were collected from the eye retro-orbital plexus of rats before and also at 0.5, 1, 2, 4, 6, 8 and 12 h after drug administration and the samples were analyzed for blood glucose by using glucose-oxidase/peroxidase method using a visible spectrophotometer. In long term study, the extract (300 mg/kg) was administered to streptozotocin-induced diabetic rats, daily for 8 weeks. Blood glucose was measured at weekly intervals for 4 weeks. Urine samples were collected before the induction of diabetes and at the end of 8 weeks of treatments and analyzed for urinary protein, albumin and creatinine levels. The data was compared statistically using one-way ANOVA with post-hoc Dunnet's t-test.ResultsThe chloroform extract of T. chebula seeds produced dose-dependent reduction in blood glucose of diabetic rats and comparable with that of standard drug, glibenclamide in short term study. It also produced significant reduction in blood glucose in long term study. Significant renoprotective activity is observed in T. chebula treated rats. The results indicate a prolonged action in reduction of blood glucose by T. chebula and is probably mediated through enhanced secretion of insulin from the β-cells of Langerhans or through extra pancreatic mechanism. The probable mechanism of potent renoprotective actions of T. chebula has to be evaluated.ConclusionThe present studies clearly indicated a significant antidiabetic and renoprotective effects with the chloroform extract of T. chebula and lend support for its traditional usage. Further investigations on identification of the active principles and their mode of action are needed to unravel the molecular mechanisms involved in the observed effects.

The marine environment is an exceptional reservoir of bioactive natural products having potential biomedical applications, many of which differ from those of terrestrial organisms in both chemical structures and peculiarities of biological actions.1) Several marine natural products have become the source of potentially novel chemical leads for the ongoing global search of therapeutic agents for the treatment of multiple disease categories. Majority of marine natural products and their derivatives are produced by invertebrates such as sponges, soft corals, tunicates, mollusks or bryozoans and currently in advanced preclinical evaluation.Many compounds were reported from marine sources, having anti-inflammatory activity. Amomg them manoalide, a sesterterpene isolated from the sponge Luffariella variabilis 2) found to have a selective anti-inflammatory profile.3)The pseudopterosins 4,5) are a family of natural products produced by sea whips in Florida and the Bahamas, also show anti-inflammatory activity. These compounds are extremely potent chemicals in reducing swellings and skin irritations and accelerating wound healing.3) A sesterterpene, palaulol, from the sponge Fascaplysinopsis sp., 6) a sesquiterpene furan from the coelenterate, Sinularia sp. 7) and the ceramide isolated from the tunicate Cystodytes cf. dellechiajei 8) are some other anti-inflammatory agents.Since non-steroidal compounds and sphingosine 8) derivatives were reported to have significant anti-inflammatory activity, and some of them have even entered into the clinical trial, the new sphingosine derivative (1) and the cembrenoid diterpene (2) obtained from soft corals of Sinularia crassa TIXIER-DURIVAULT and Lobophytum species respectively were evaluated for their anti-inflammatory activity. It was already reported that this diterpene has cytotoxic 9) and anti-HIV 10) activities. But so far no anti-inflammatory activity was reported. This is the first report of sphingosine derivative having anti-inflammatory activity from soft corals. MATERIALS AND METHODS Collection of Soft CoralsThe soft corals Sinularia crassa TIXIER-DURIVAULT and Lobophytum sp., were collected in March 1993, on the coasts of the Andaman and Nicobar Islands [Kalipur (Diglipur) and Natkal Islands 93°02ЈE, 13°20ЈN] by hand picking at 1 m depth in the inter-tidal rocky region. The animals were collected in plastic net bags and brought to the shore, washed with fresh water, cut into thin slices and preserved in ethanol in plastic carboy. The large specimens with clear morphological features were separately preserved in ethanol in small plastic container for identification purpose. The organisms were brought to the laboratory for processing.Identification The soft corals were identified as Sinularia crassa TIXIER-DURIVAULT and Lobophytum sp., through Visakhapatnam-530 003, Andhra Pradesh, India: and c Pharmacology Division, GITAM Dental College; Visakhapatnam-530 045, Andhra Pradesh, India. Received February 7, 2005; accepted April 15, 2005 The aim of this study is to determ...

The role of matrix metalloproteinase-12 (MMP-12) in the pathogenesis of several inflammatory diseases such as chronic obstructive pulmonary disease, emphysema, and asthma is well established. Several new studies and recent reports from our laboratory and others highlighted the detrimental role of MMP-12 in the pathogenesis of several neurological diseases. In this review, we discuss in detail the pathological role of MMP-12 and the possible underlying molecular mechanisms that contribute to disease pathogenesis in the context of central nervous system diseases such as stroke, spinal cord injury, and multiple sclerosis. The available information on the specific MMP-12 inhibitors used in several preclinical and clinical studies is also reviewed. Based on the reported studies to date, MMP-12 suppression could emerge as a promising therapeutic target for several CNS diseases that were discussed in this review.

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Background/Aims: Stem cell treatment is one of the potential treatment options for ischemic stroke. We recently demonstrated a protective effect of human umbilical cord blood-derived mesenchymal stem cells (HUCB-MSCs) in a rat model of ischemic stroke. The treatment attenuated apoptosis and prevented DNA damage. A collection of published studies, including several from our laboratory, indicated the induction and detrimental role for several matrix metalloproteinases (MMPs) in post-stroke brain injury. We hypothesized that the HUCB-MSCs treatment after focal cerebral ischemia prevents the dysregulation of MMPs and induces the expression of endogenous tissue inhibitors of metalloproteinases (TIMPs) to neutralize the elevated activity of MMPs. Methods: To test our hypothesis, we administered HUCBMSCs (0.25 million cells/animal and 1 million cells/animal) intravenously via tail vein to male Sprague-Dawley rats that were subjected to a transient (two-hour) right middle cerebral artery occlusion (MCAO) and one-day reperfusion. Ischemic brain tissues obtained from various groups of rats seven days after reperfusion were subjected to real-time PCR, immunoblot, and immunofluorescence analysis. Results: HUCB-MSCs treatment prevented the induction of MMPs, which were upregulated in ischemia-induced rats that received no treatment. HUCBMSCs treatment also prevented the induction of TIMPs expression. The extent of prevention of MMPs and TIMPs induction by HUCB-MSCs treatment is similar at both the doses tested. Conclusion: Prevention of stroke-induced MMPs upregulation after HUCB-MSCs treatment is not mediated through TIMPs upregulation.