G. K. Patnaik

Curcumin enhances wound healing in streptozotocin induced diabetic rats and genetically diabetic mice

Tissue repair and wound healing are complex processes that involve inflammation, granulation and tissue remodeling. Interactions of different cells, extracellular matrix proteins and their receptors are involved in wound healing, and are mediated by cytokines and growth factors. Previous studies from our laboratory have shown that curcumin (diferuloylmethane), a natural product obtained from the rhizomes of Curcuma longa, enhanced cutaneous wound healing in rats and guinea pigs. In this study, we have evaluated the efficacy of curcumin treatment by oral and topical applications on impaired wound healing in diabetic rats and genetically diabetic mice using a full thickness cutaneous punch wound model. Wounds of animals treated with curcumin showed earlier re‐epithelialization, improved neovascularization, increased migration of various cells including dermal myofibroblasts, fibroblasts, and macrophages into the wound bed, and a higher collagen content. Immunohistochemical localization showed an increase in transforming growth factor‐β1 in curcumin‐treated wounds compared to controls. Enhanced transforming growth factor‐β1 mRNA expression in treated wounds was confirmed by in situ hybridization, and laser scan cytometry. A delay in the apoptosis patterns was seen in diabetic wounds compared to curcumin treated wounds as shown by terminal deoxynucleotidyl transferase–mediated deoxyuridyl triphosphate nick end labeling analysis. Curcumin was effective both orally and topically. These results show that curcumin enhanced wound repair in diabetic impaired healing, and could be developed as a pharmacological agent in such clinical settings.

Enhancement of wound healing by curcumin in animals

Tissue repair and wound healing are complex processes that involve inflammation, granulation, and remodeling of the tissue. In this study, we evaluated the in vivo effects of curcumin (difeurloylmethane), a natural product obtained from the rhizomes of Curcuma longa on wound healing in rats and guinea pigs. We observed faster wound closure of punch wounds in curcumin‐treated animals in comparison with untreated controls. Biopsies of the wound showed reepithelialization of the epidermis and increased migration of various cells including myofibroblasts, fibroblasts, and macrophages in the wound bed. Multiple areas within the dermis showed extensive neovascularization, and Massons Trichrome staining showed greater collagen deposition in curcumin‐treated wounds. Immunohistochemical localization of transforming growth factor‐β1 showed an increase in curcumin‐treated wounds as compared with untreated wounds. In situ hybridization and polymerase chain reaction analysis also showed an increase in the mRNA transcripts of transforming growth factor‐β1 and fibronectin in curcumin‐treated wounds. Because transforming growth factor‐β1 is known to enhance wound healing, it may be possible that transforming growth factor‐β1 plays an important role in the enhancement of wound healing by curcumin.

Depletion of reduced glutathione, ascorbic acid, vitamin E and antioxidant defence enzymes in a healing cutaneous wound.

In the present investigation the involvement of free radicals in a self-healing cutaneous wound has been demonstrated. The levels of different enzymatic and non-enzymatic antioxidants have been studied in 2,4,7 and 14 days old wounds and compared with normal skin. Except for glutathione reductase (GR), all other enzymatic and non-enzymatic antioxidants were found to decrease following wounding. The decrease was 60-70% in superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione-S-transferase (GST) at 2, 4 and 7 days, while in the case of catalase (CAT) the decrease was 40-60% during this period. Although a complete recovery in the activity of CAT was observed, SOD and GPx did not recover completely and GST was found to be slightly elevated on 14th day post wounding. Non-enzymatic antioxidants viz, ascorbic acid, vitamin E and glutathione were also found to decrease to about 60-70% and except glutathione none of them was found to recover completely at 14th day postwounding. Interestingly thiobarbituric acid reactive substance (TBARS) expressed as malondialdehyde (MDA) equivalent, a marker of lipid peroxidation, decreased following wounding which could be because of meagre availability of lipid substrate and/or of ascorbic acid. The results indicate that wounding results in loss of different free radical scavengers both enzymatic and non-enzymatic which either partially or completely recover following healing.

Hepatoprotective Activity of Ricinus communis Leaves

AbstractRicinus communis (leaf extract) was evaluated for hepatoprotective, choleretic and anticholestatic activity. In a preliminary test with albino rats, an ethanol extract showed significant protection against galactosamine-induced hepatic damage. It also showed dose-dependent choleretic and anti cholestatic activity, and hepatoprotective activity as judged by hepatocytes isolated from paraceta mol-treated rats. On fractionation of the ethanol extract, maximum activity was localised in the butanol fraction. Subsequent chromatographic fractionation and testing in the galactosamine model led to the isolation of two active fractions which in turn yielded two pure compounds: ricinine and N-demethyl-ricinine. N-Demethyl-ricinine was found to be more active and it reversed the biochemical changes produced by galactosamine at a dose of 6 mg/kg x 7 days. It possessed marked choleretic activity and demonstrated an anticholestatic effect against paracetamol-induced cholestasis.

Morphine-induced straub tail response : mediated by central μ2-opioid receptor

The opioid receptor mechanism involved in the morphine induced straub tail response was investigated in mice. Morphine (2.5, 5, 10 and 20 mg/kg s.c.) produced a dose dependent straub tail response and analgesia (hot plate test). Naloxone (5 mg/kg s.c.) and the mu-opioid receptor antagonist beta-funaltrexamine (10 micrograms i.c.v.) blocked both the straub tail response and analgesia while the mu 1-opioid receptor selective antagonist naloxonazine (35 mg/kg s.c.) blocked only analgesia and did not affect the straub tail response. Morphine (20 micrograms) administered by the i.c.v. route also produced the straub tail response as well as analgesia. Pretreatment with naloxonazine (35 mg/kg s.c.) antagonised i.c.v. administered morphine induced analgesia while the straub tail response was not affected. The results indicate that the morphine induced straub analgesia while the straub tail response was not affected. The results indicate that the morphine induced straub tail response is mediated by central mu 2-opioid receptors.

Immunomodulatory Effect of Albizzia Lebbeck

The immunomodulatory effect of the bark of Albizzia lebbeck (Sirisha) was evaluated by studying humoral and cell mediated immune responses. The hot aqueous extract and its butanolic fraction were administered once daily for one week in mice, immunised previously with sheep red blood cells (SRBC). At the dose levels tested (6.25, 12.5 and 25 mg/kg, p.o.), A. lebbeck treated mice developed higher serum antibody titres compared to the vehicle treated group and the effect was comparable to the standard drug muramyl dipeptide (MDP). Delayed type hypersensitivity response was suppressed in SRBC immunised mice treated with A. lebbeck extract. The macrophage migration index remained unaltered in both mice and rats. These results are discussed in the light of possible immunopotentiating effects of A. lebbeck.

Evaluation of Antiurolithiatic Activity of Tribulus Terrestris

AbstractTribulus Terrestris (Fruit) Has Been Used Widely In The Ayurvedic System Of Medicine For The Treatment Of Various Urinary Disorders Including Urolithiasis. In Order To Evaluate The Therapeutic Claims Made For This Plant In Traditional Medicine, The Ethanol Extract Of T. Terrestris (Fruit) Was Tested For Activity Against Artificially Induced Urolithiasis In Albino Rats. The Extract Was Administered At Daily Oral Doses Of 25, 50 and 100 Mg/Kg For 4 Months. It Exhibited Dose-Dependent Antiurolithiatic Activity and Almost Completely Inhibited Stone Formation. Other Biochemical Parameters In Urine and Serum, and The Histopathology Of Urinary Bladder, Which Were Altered During The Process Of Stone Formation, Were Also Normalized By The Plant Extract In A Dose-Dependent Manner. These Observations Thus Substantiate The Traditional Claim. Further Detailed Study Is In Progress To Isolate The Active Principle(S) and To Establish Their Mode(S) Of Action.

Hepatoprotective effect of picroliv against rifampicin-induced toxicity

Picroliv, the active constituent of the plant Picrorhiza Kurroa, showed significant hepatoprotective as well as anticholestatic activity against rifampicin‐induced hepatic damage. Rifampicin (50 mg/kg ip × 6 days) resulted in the reduction of bile flow as well as its contents (bile salts and bile acids) in the conscious rat and anesthetized guinea pig. Further, it also caused a decrease in the viability and rate of oxygen consumption in isolated rat hepatocytes. Picroliv treatment significantly reversed the altered parameters of bile and hepatocytes. The hepatoprotective drug silymarin on comparison was found to be less active than picroliv. Drug Dev. Res. 40:299–303, 1997.

Synthesis and biological evaluation of 2-[substituted acetyl]amino-5-alkyl-1,3,4-thiadiazoles

Abstract Some new N-substituted acetyl derivatives of 2-amino-5-alkyl-1,3,4-thiadiazoles have been prepared and investigated for antihistaminic and spasmolytic activity on guine pig ileum. A few of the compounds showed encouraging effects. In addition, some of the compounds also showed anti-inflammatory activity.

Morphine like activity of some new met-enkephalin analogues☆

Abstract (D-Ala 2 , Met 5 )-Enkephalin-N-alkylamides were synthesised and tested for inhibition of electrically stimulated contraction of isolated guinea pig ileum and for analgesic activity in mice. The isopropylamide derivative had maximum activity by icv but not by ip route whereas n -propylamide had similar potency by both the routes and produced less respiratory depression than morphine in anaesthetised cats.