Assessment of Antihyperlipidemic and Antitumor Effect of Isolated Active Phytoconstituents from Apium graveolens L. through Bioassay-Guided Procedures.

The seeds of A. graveolens yielded coumarin derivatives such as seselin, methoxsalen, and 3H-isobenzofuran-1-one through chromatographic separation techniques. The structure of the components has been established on the basis of spectral data analysis. The present study was undertaken to explore the antihyperlipidemic and antitumor effects of ethanolic extract and phytoconstituents of A. graveolens in rodents. Albino rats were administered intraperitoneal (i.p.) injection of Triton WR 1339 for the induction of hyperlipidemia at a dose of 400 mg/kg body weight. After 24 h of Triton administration, the test drugs were administered orally at dose of 50 mg/kg body weight in rats. The extract and isolated components were further investigated for the tumor take inhibitory activity in hybrid mice (of C57BL strain + Swiss albino strain). Preventive group animals were injected daily with the extract and isolated components at a dose of 50 mg/kg body weight i.p. for 10 consecutive days. The animals were observed for the growth of tumor after injection of B16F10 melanoma cells into the dorsal skin of mice. The study showed significant reduction in total cholesterol (p < .001), triglycerides (p < .001) and low-density lipoprotein (LDL) level (bp < .01) and significantly increased high density lipoprotein (HDL) level (p < .01) after the treatment. Pretreatment showed delay in tumor growth by increasing the volume-doubling time (p < .01), growth delay (p < .01), and mean survival time (p < .001). Acute treatment caused stimulatory effect on HDL level and inhibition in total cholesterol (TC) and triglyceride (TG) elevation induced by Triton. Tumor regression studies showed a regression response for tumor growth in vivo of murine mouse melanoma tumor cell lines.

Effect of Ipomea carnea Jacq. flowers on hematological changes in toluene diisocyanate-induced inflammation in Wistar rats.

AIM: To investigate the active chloroform fraction of the ethanol extract of Ipomoea carnea flowers on hematological changes in toluene diisocyanate-induced inflammation in Wistar rats. METHOD: Except for the control group, all of the rats were sensitized with intranasal application of 5 µL of 10% toluene diisocyanate (TDI) for 7 days. One week after second sensitization, all of the rats were provoked with 5 µL of 5% TDI to induce airway hypersensitivity. After the last challenge, blood and bronchoalvelor lavage (BAL) fluid were collected and subjected to total and differential leucocytes count. Flash chromatography was performed on the most active chloroform fraction to isolate an individual component. RESULTS: Treatment with the ethanolic extract and its chloroform fraction at an oral dose of 200 mg·kg⁻¹ showed a significant decrease in circulating neutrophil and eosinophil in blood and BAL as compared with standard dexamethasone (DEXA). The structure of the compound obtained from chloroform fraction of Ipomea carnea was elucidated as stigmast-5, 22-dien-3ß-ol on the basis of spectral data analysis. CONCLUSION: The chloroform fraction was found to be more effective to suppress airway hyper reactivity symptoms, and decreased count of both total and differential inflammatory cells.

Evaluation of antihyperlipidemic and antitumor activities of isolated coumarins from Salvadora indica.

CONTEXT: Salvadora indica Wight (Salvadoraceae) contains a number of medically beneficial properties including abrasives, astringents and antiseptics. Traditionally, it was used by ancient Arabs to whiten and polish teeth. OBJECTIVE: This study explores the antihyperlipidemic and antitumor effects of an ethanol extract of S. indica and its isolated phytoconstituents in rodents. MATERIAL AND METHODS: Flash chromatography was used for the isolation of phytoconstituents from the stems of S. indica. An antihyperlipidemic study was carried out in Triton loaded rats. Animal groups were given intraperitoneal (i.p.) injection of Triton WR 1339 at dose of 400 mg/kg body weight (b.w.). Furthermore, antitumor activity was investigated in hybrid mice (of C57BL strain + Swiss albino strain). The animals were observed for tumor growth after injection of B16F10 melanoma cells into the dorsal skin of mice. RESULTS: The stems of S. indica yielded xanthotoxin and umbelliferone through chromatographic separation techniques. The structures of the compounds were elucidated by spectroscopic data interpretation and showed antihyperlipidemic activity. The study showed significant reduction in total cholesterol (TC) (p < 0.01), triglycerides (TGs) (p < 0.001), low-density lipoproteins (p < 0.01) level whereas increased in high-density lipoprotein (p < 0.01) at a significant level, after the treatment. Pretreatment with the extract and phytoconstituents also showed delayed tumor growth by increasing the volume doubling time (VDT) (p < 0.01), growth delay (GD) (p < 0.01) and mean survival time (p < 0.001). DISCUSSION AND CONCLUSION: Acute treatment caused a stimulatory effect on high density lipoprotein level and inhibition in TC and TG elevation induced by Triton. Tumor regression studies showed a regression response for tumor growth in vivo of murine mouse melanoma as demonstrated by increasing the VDT and GD.

Isolation of bioactive phytoconstituent from Alpinia galanga L. with anti-hyperlipidemic activity.

The present study was undertaken to explore the antihyperlipidemic effect of ethanolic extract of rhizomes of Alpinia galanga L. and its chloroform fraction in Triton-induced hyperlipidemic rats. Bioactivity guided fractionation was followed by chromatographic studies. Flash chromatography was done for the most active fraction resulting in the isolation of 5-(hydroxymethyl) furfural. Animals were administered with i.p. injection of Triton WR 1339 at dose of 400 mg/kg body weight. After 24 hr of Triton administration, the ethanolic extract and its fraction were administered orally at doses of 200 and 400 mg/kg body weight in rats. The treatment was continued for 5 days with a view to see the effect on lipid profile. Serum samples were subjected to biochemical analysis. The study dose dependently inhibited the total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL) level, and significantly increased high-density lipoprotein (HDL) level. Phytochemical screening revealed the presence of tannins, coumarins, flavanoids, sterols, and glycosides. Phytochemical investigation of the chloroform fraction of A. galanga L. resulted in the isolation of 5-(hydroxymethyl) furfural. UV λmax was found to be 276 nm for the isolated component. Acute treatment caused a stimulatory effect on the HDL level and inhibition in TC and TG elevation induced by triton.

Effect of ether- and water-soluble fractions of Carica papaya ethanol extract in experimentally induced hyperlipidemia in rats.

CONTEXT: The papaya is the fruit of the plant Carica papaya L. (Caricaceae) used in India. Fruit and latex are both rich in an enzyme called papain. It is used as a folk remedy for contraception and abortion. OBJECTIVE: The present study explored the anti-hyperlipidemic effect of the ether- and water-soluble fractions of C. papaya ethanol extract in olive oil-induced hyperlipidemic rats. The study also involved chromatographic studies of extract and fractions. MATERIALS AND METHODS: Flash chromatography was done for the most active fraction. The extract and fractions were administered orally at doses of 200 and 400 mg/kg body weight in rats. Olive oil (5 mL/kg oral dose) was administered 30 min after treatment. Blood was collected and centrifuged at 3000 rpm for 15-20 min and subjected to biochemical analysis. RESULT: The study dose-dependently inhibited the total cholesterol (TC), triglycerides (TG), low-density lipoproteins (LDL) level, and significantly increased high-density lipoprotein (HDL) level. Phytochemical screening revealed the presence of fats in the ether fraction, whereas the water fraction revealed the presence of tannins, alkaloids, glycosides. UV λ(max) was found to be 217 nm with a melting point of 41°C for the isolated component. DISCUSSION AND CONCLUSION: The anti-hyperlipidemic effect was evaluated in olive oil-loaded rats. Acute treatment caused stimulatory effect on HDL level and inhibition in TC and TG elevation induced by olive oil. The extract and water fraction showed protective action by increasing the HDL cholesterol level.

Depot based drug delivery system for the management of depression.

Depression is a common mental disorder discerns with depressed mood, loss of interest, the primary treatment methods are drug therapy, electroconvulsive therapy, psychotherapy, light therapy, vagus nerve stimulation, etc. A number of innovative delivery systems have been developed to address suboptimal therapy outcomes by enhancing drug delivery, assuring efficacy of treatment, reducing side effects, improving compliance and drug targeting specific locations resulting in a higher efficiency. Depot delivery offers the advantage of a very high loading, controlled release of drug for an extended period of time and reduces frequency of dosing. The increase in AUC and decrease in Cmax reflects that the depot formulations could reduce the toxic complications and limitations of conventional and oral therapies. Products at preclinical and clinical stages include formulations of naltrexone and buprenorphine for alcoholism/drug abuse, GLP-1 peptides for diabetes, r-hFSH for fertility, dopamine for nerve growth, dexamethasone for ocular treatment, melanotan for cancer prevention, plasmid DNA for cancer prevention, a variety of vaccines, octreotide generics, etc. Most depot formulations are comprised of biodegradable polymer-excipients that control the rate of drug release and resorbs during/after drug release. The major advantage of depot antipsychotics over oral medication was facilitation of compliance in medication taking. One class of biodegradable polymers that has gained wide acceptance and still attractive today is lactide/glycolide polymers. The greatest advantage of these degradable polymers is that they are broken down into biologically acceptable molecules that are metabolized and removed from the body via normal metabolic pathways. This versatile delivery system offers the advantage of a very high loading and controlled release of various drug for an extended period of time compared with plain delivery system. New formulations of depression can offer advantages over older formulations in terms of convenience, side effect profiles, efficacy, and/or a fast onset of action.

Effect of chloroform and aqueous basic fraction of ethanolic extract from Apium graveolens L. in experimentally-induced hyperlipidemia in rats.

The present study was undertaken to explore the antihyperlipidemic effect of ethanolic extract of seeds of Apium graveolens L. and its chloroform and aqueous basic fraction in olive oil induced hyperlipidemic rats. The antihyperlipidemic activity of Apium graveolens was compared with a standard drug Atrovastatin (50mg/kg). The study involved phytochemical screening and chromatographic studies of extract and fractions. The ethanolic extract and its fractions were administered orally at doses of 200 and 400 mg/kg body weight in rats. Olive oil (5ml/kg oral dose) was administered 30 min after treatment. Blood was collected by ocular puncture 2 and 4 h after olive oil treatment and centrifuged at 3000 rpm for 15-20 min. Serum samples were further subjected to biochemical analysis. The study dose dependently inhibited the total cholesterol (TC) triglycerides (TG), low density lipoproteins (LDL) level, and significantly increased high density lipoprotein (HDL) level. Phytochemical screening revealed the presence of terpenoid, tannin, alkaloid, glycoside, flavanoid and sterols. UV λmax was found to be 206 nm with a melting point of 137-138°C for the isolated component. The antihyperlipidemic effect was evaluated in olive oil loaded rats. Acute treatment caused stimulatory effect on HDL level and inhibition in TC and TG elevation induced by olive oil.

Development and characterization of in situ gel system for nasal insulin delivery.

The objective of the present study was to develop a thermosensitive in situ gel system based on chitosan and poly vinyl alcohol (PVA) for nasal delivery of insulin. The hydrogel was prepared by mixing chitosan and PVA. The concentration of the components was optimized during formulation development. The prepared hydrogel was characterized for gelation temperature, gelation time, viscosity changes, degree of swelling, in vitro release and in vivo hypoglycemic effect. The prepared hydrogel was liquid at room temperature while underwent thermal transition from solution below or at room temperature to non-flowing hydrogel when incubated at 37 degrees C for approximately 12 minutes with increased viscosity. The in vitro release of insulin from gel network was observed spectrophotometrically which was good enough to maintain blood glucose level for six hour. Furthermore, the formulation when evaluated for their in vivo hypoglycemic effect, demonstrated its ability to reduce glucose level. The observed in vitro and in vivo results indicate that the proposed thermosensitive in situ gelling system has substantial potential as nasal delivery system for insulin.

Evaluation and optimization of preparative variables for controlled-release floating microspheres of levodopa/carbidopa.

Levodopa, a prodrug of dopamine, is the first line drug in the treatment of Parkinson's disease. All current levodopa products are formulated in combination with aromatic amino acid decarboxylase inhibitors such as carbidopa or benserazide to prevent the peripheral metabolism of levodopa. The objective of the present investigation was to produce floating microspheres of carbidopa (CD)/levodopa (LD) to enhance their efficacy by increasing their gastric residence time, which is major technique to improve efficacy of narrow absorption window drugs. The microspheres were prepared by the o/w emulsion-solvent diffusion method using polymers hydroxypropylmethyl cellulose K15 M (HPMC K15 M) and ethyl cellulose (EC). The effects of various formulation and process variables on the particle size, in vitro floating behavior, percent drug entrapment, and in vitro drug release were studied. The size and surface morphology of prepared microspheres were characterized by optical and scanning electron microscopy, respectively. In vitro drug release studies were performed and drug release kinetics was evaluated using the linear regression analysis. The prepared microspheres exhibited prolonged drug release (approximately 10h) and remained buoyant for >12 h. Spherical and smooth-surfaced microspheres with encapsulation efficiency ranging from 43% to 80% were obtained. In vitro studies demonstrated diffusion-controlled drug release from the microspheres.

A potential of some medicinal plants as an antiulcer agents.

Peptic ulcers are a broad term that includes ulcers of digestive tract in the stomach or the duodenum. The formation of peptic ulcers depends on the presence of acid and peptic activity in gastric juice plus a breakdown in mucosal defenses. There are two major factors that can disrupt the mucosal resistance to injury: non-steroidal antiinflammatory drugs (NSAIDs) example, aspirin and Helicobacter pylori infection. Numerous natural products have been evaluated as therapeutics for the treatment of a variety of diseases, including peptic ulcer. There has been considerable pharmacological investigation into the antiulcer activity of some compounds. In this work, we shall review the literature on different medicinal plant and alkaloids with antiulcer activity. This article reviews the antiacid/anti-peptic, gastroprotective and/or antiulcer properties of the most commonly employed herbal medicines and their identified active constituents. The experimental parameters used for antiulcer activity were cold restraint stress-induced ulcer model, Diclofenac-induced ulcer model in rats, (HCl-ethanol)-induced ulcer in mice and water immersion stress-induced ulcer in rats. The ideal aims of treatment of peptic ulcer disease are to relieve pain, heal the ulcer and delay ulcer recurrence. About 70% of patients with peptic ulcer disease are infected by Helicobacter pylori and eradication of this microorganism seems to be curative for this disease. This article reviews drugs derived from medicinal plant more commonly used in the world for peptic ulcer and, if reported, the antiulcer activity. This article will be concerned only with the antiulcer and gastro-protective effects.

Effect of Evolvulus alsinoides Linn. on learning behavior and memory enhancement activity in rodents.

In the Ayurvedic system of medicine, the whole herb of 'Shankhpushpi' has been employed clinically for centuries for its memory potentiating, anxiolytic and tranquilizing properties. The present study was undertaken to investigate the effects of Evolvulus alsinoides (EA), considered as Shankhpushpi on learning and memory in rodents. Nootropic activity using Cook and Weidley's pole climbing apparatus, passive avoidance paradigms and active avoidance tests were used to test learning and memory. The ethanol extract of EA and its ethyl acetate and aqueous fractions were evaluated for their memory enhancing properties. Two doses (100 and 200 mg/kg p.o.) of the ethanol extract and ethyl acetate and aqueous fractions were administered in separate groups of animals. Both doses of all the extracts of EA significantly improved learning and memory in rats. Furthermore, these doses significantly reversed the amnesia induced by scopolamine (0.3 mg/kg i.p.). Nootropic activity was compared using piracetam as the standard. EA also exhibited potent memory enhancing effects in the step-down and shuttle-box avoidance paradigms.

Effect of ethanolic extract of Cassia occidentalis Linn. for the management of alloxan-induced diabetic rats.

AIM: As per traditional claims, root, bark, leaf and flower of the plant Cassia occidentalis Linn. (Caesalpiniaceae) have been reported to possess antidiabetic activity. Based on this traditional indication, the aim of this study was to evaluate the antidiabetic activity of ethanolic extract of C. occidentalis in normal and alloxan induced diabetic rats. MATERIALS AND METHODS: Ethanolic extract of the whole plant of C. occidentalis was orally tested at doses of 100 and 200 mg/kg for evaluating the hypoglycemic effect in normal and alloxan-induced diabetic rats. In addition, changes in body weight, serum cholesterol, triglyceride and total protein levels, assessed in the ethanol extract treated diabetic rats were compared with diabetic control and normal animals. Histopathologic observations during 21 days of treatment were also evaluated. RESULTS: Ethanolic extract of C. occidentalis produced a significant reduction in fasting blood glucose levels in the normal and alloxan-induced diabetic rats at doses of 100 and 200 mg/kg body weight. Treatment with ethanolic extract of C. occidentalis in normal and alloxan-induced diabetic rats led to a dose-dependent fall in blood sugar levels. Significant differences were observed in serum lipid profiles (cholesterol and triglyceride), serum protein and changes in body weight in ethanolic extract treated diabetic animals, when compared with the diabetic control and normal animals. Concurrent histopathologic studies of the pancreas of these animals showed comparable regeneration by ethanolic extract, which were earlier necrosed by alloxan. CONCLUSION: Ethanolic extract of C. occidentalis exhibited significant antidiabetic activity in normal and alloxan-induced diabetic rats. The rats also showed improvement in parameters like body weight and lipid profiles and also, histopathologic studies showed regeneration of ß-cells of pancreas and so it might be of value in the treatment of diabetes.

Wound healing potential of methanolic extract of Trichosanthes dioica Roxb (fruits) in rats.

AIM OF THE STUDY: The present study provides a scientific evaluation for the wound healing potential of methanolic (MeOH) extract of TDR fruits. MATERIALS AND METHODS: Excision and incision wounds were inflicted upon three groups of six rats each. Group I was assigned as control (ointment base), Group II was treated with standard silver sulfadiazine (0.01%) cream. Group III was treated with 5% MeOH extract ointment. The parameters observed were percentage of wound contraction, epithelialization period, hydroxyproline content, tensile strength including histopathological studies. RESULTS: It was noted that the effect produced by the extract ointment showed significant (P<0.01) healing in both the wound models when compared with control group. All parameters such as wound contraction, epithelialization period, hydroxyproline content, tensile strength and histopathological studies showed significant changes when compared to control. CONCLUSION: The result shows that TDR extract ointment demonstrates wound healing potential in both excision and incision models.

Effect of Convulvulus pluricaulis Choisy. on learning behaviour and memory enhancement activity in rodents.

The present study was undertaken to investigate the effects of Convulvulus pluricaulis (CP), considered as Shankhpushpi on learning and memory in rodents. Nootropic activity using Cook and Weidley's Pole Climbing Apparatus, passive avoidance paradigms and active avoidance tests were used to test learning and memory. The ethanolic extract of CP and its ethyl acetate and aqueous fractions were evaluated for their memory enhancing properties. Two doses (100 and 200 mg kg(-1) p.o.) of the ethanolic extract and ethyl acetate and aqueous fractions were administered in separate groups of animals. Both the doses of all the extracts of CP significantly improved learning and memory in rats. Furthermore, these doses significantly reversed the amnesia induced by scopolamine (0.3 mg kg(-1) i.p.). Nootropic activity was compared using piracetam as the standard. Moreover, CP has exhibited potent memory-enhancing effects in the step-down and shuttle-box avoidance paradigms. Further studies are necessitated to identify the exact mechanism of action.