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Fulltext Acute toxicity and gastroprotective role of M. pruriens in ethanol-induced gastric mucosal injuries in rats

Golbabapour S, Hajrezaie M, Hassandarvish P, Abdul Majid N, Hadi AH, Nordin N, et al.

Biomed Res Int, 2013;2013:974185.
PMID: 23781513 DOI: 10.1155/2013/974185

The investigation was to evaluate gastroprotective effects of ethanolic extract of M. pruriens leaves on ethanol-induced gastric mucosal injuries in rats. Forty-eight rats were divided into 8 groups: negative control, extract control, ulcer control, reference control, and four experimental groups. As a pretreatment, the negative control and the ulcer control groups were orally administered carboxymethylcellulose (CMC). The reference control was administered omeprazole orally (20 mg/kg). The ethanolic extract of M. pruriens leaves was given orally to the extract control group (500 mg/kg) and the experimental groups (62.5, 125, 250, and 500 mg/kg). After 1 h, CMC was given orally to the negative and the extract control groups. The other groups received absolute ethanol. The rats were sacrificed after 1 h. The ulcer control group exhibited significant mucosal injuries with decreased gastric wall mucus and severe damage to the gastric mucosa. The extract caused upregulation of Hsp70 protein, downregulation of Bax protein, and intense periodic acid schiff uptake of glandular portion of stomach. Gastric mucosal homogenate showed significant antioxidant properties with increase in synthesis of PGE2, while MDA was significantly decreased. The ethanolic extract of M. pruriens leaves was nontoxic (<5 g/kg) and could enhance defensive mechanisms against hemorrhagic mucosal lesions.

Matched MeSH terms: Plant Extracts/pharmacology*; Plant Extracts/therapeutic use
In vivo hepatoprotective effect of Morinda elliptica stem extract against liver fibrosis induced by thioacetamide

Bradosty SW, Hamad SW, Agha NFS, Shaikh FK, Qadir Nanakali NM, Aziz PY, et al.

Environ Toxicol, 2021 Dec;36(12):2404-2413.
PMID: 34436826 DOI: 10.1002/tox.23353

Morinda elliptica L. (Rubiaceae) is a phytomedicinal herb, used to treat gastrointestinal complications in Peninsular Malaysia. The study evaluates the in vivo hepatoprotective activity of ethanolic extract of M. elliptica stem in thioacetamide (TAA) induced liver fibrosis in male Sprague Drawly rats. Thirty adult rats were divided into five groups of six rats each. Rats of the normal control group received intraperitoneal injections (i. p.) of vehicle 10% Tween-20, 5 ml/kg, and hepatotoxic group 200 mg/kg TAA three times per week respectively. Three supplementary groups were treated with TAA plus daily oral silymarin (50 mg/kg) or M. elliptica (250 or 500 mg/kg). After 8 weeks of treatment, all rats were sacrificed. Liver fibrosis was assessed by gross macroscopic and microscopic tissue analysis, histopathological, and biochemical analysis. The livers of the TAA treated group showed uniform coarse granules, hepatocytic necrosis with lymphocytes infiltration. Contrary, the livers of M. elliptica treated groups (250 and 500 mg/kg) were much smoother and the cell damage was much lesser. The livers of M. elliptica treated groups rats showed elevated activity of SOD and CAT with a significant decrease in MDA level at p

Matched MeSH terms: Plant Extracts/pharmacology
Fulltext In vivo antioxidant and antiulcer activity of Parkia speciosa ethanolic leaf extract against ethanol-induced gastric ulcer in rats

Al Batran R, Al-Bayaty F, Jamil Al-Obaidi MM, Abdualkader AM, Hadi HA, Ali HM, et al.

PLoS One, 2013;8(5):e64751.
PMID: 23724090 DOI: 10.1371/journal.pone.0064751

BACKGROUND: The current study was carried out to examine the gastroprotective effects of Parkia speciosa against ethanol-induced gastric mucosa injury in rats.
METHODOLOGY/PRINCIPAL FINDINGS: Sprague Dawley rats were separated into 7 groups. Groups 1-2 were orally challenged with carboxymethylcellulose (CMC); group 3 received 20 mg/kg omeprazole and groups 4-7 received 50, 100, 200 and 400 mg/kg of ethanolic leaf extract, respectively. After 1 h, CMC or absolute ethanol was given orally to groups 2-7. The rats were sacrificed after 1 h. Then, the injuries to the gastric mucosa were estimated through assessment of the gastric wall mucus, the gross appearance of ulcer areas, histology, immunohistochemistry and enzymatic assays. Group 2 exhibited significant mucosal injuries, with reduced gastric wall mucus and severe damage to the gastric mucosa, whereas reductions in mucosal injury were observed for groups 4-7. Groups 3-7 demonstrated a reversal in the decrease in Periodic acid-Schiff (PAS) staining induced by ethanol. No symptoms of toxicity or death were observed during the acute toxicity tests.
CONCLUSION: Treatment with the extract led to the upregulation of heat-shock protein 70 (HSP70) and the downregulation of the pro-apoptotic protein BAX. Significant increases in the levels of the antioxidant defense enzymes glutathione (GSH) and superoxide dismutase (SOD) in the gastric mucosal homogenate were observed, whereas that of a lipid peroxidation marker (MDA) was significantly decreased. Significance was defined as p<0.05 compared to the ulcer control group (Group 2).

Matched MeSH terms: Plant Extracts/adverse effects; Plant Extracts/pharmacology; Plant Extracts/therapeutic use*
Fulltext In vivo evaluation of ethanolic extract of Zingiber officinale rhizomes for its protective effect against liver cirrhosis

Abdulaziz Bardi D, Halabi MF, Abdullah NA, Rouhollahi E, Hajrezaie M, Abdulla MA

Biomed Res Int, 2013;2013:918460.
PMID: 24396831 DOI: 10.1155/2013/918460

Zingiber officinale is a traditional medicine against various disorders including liver diseases.The aim of this study was to assess the hepatoprotective activity of the ethanolic extract of rhizomes of Z. officinale (ERZO) against thioacetamide-induced hepatotoxicity in rats. Five groups of male Sprague Dawley have been used. In group 1 rats received intraperitoneal (i.p.) injection of normal saline while groups 2-5 received thioacetamide (TAA, 200 mg/kg; i.p.) for induction of liver cirrhosis, thrice weekly for eight weeks. Group 3 received 50 mg/kg of silymarin. The rats in groups 4 and 5 received 250 and 500 mg/kg of ERZO (dissolved in 10% Tween), respectively. Hepatic damage was assessed grossly and microscopically for all of the groups. Results confirmed the induction of liver cirrhosis in group 2 whilst administration of silymarin or ERZO significantly reduced the impact of thioacetamide toxicity. These groups decreased fibrosis of the liver tissues. Immunohistochemistry assessment against proliferating cell nuclear antigen did not show remarkable proliferation in the ERZO-treated rats when compared with group 2. Moreover, factions of the ERZO extract were tested on Hep-G2 cells and showed antiproliferative activity (IC50 38-60 μ g/mL). This study showed hepatoprotective effect of ERZO.

Matched MeSH terms: Plant Extracts/pharmacology*
Fulltext The antiulcer effect of Cibotium barometz leaves in rats with experimentally induced acute gastric ulcer

Al-Wajeeh NS, Hajrezaie M, Al-Henhena N, Kamran S, Bagheri E, Zahedifard M, et al.

Drug Des Devel Ther, 2017;11:995-1009.
PMID: 28408799 DOI: 10.2147/DDDT.S107018

Cibotium barometz is a pharmaceutical plant customarily used in traditional medicine in Malaysia for the treatment of different diseases, such as gastric ulcer. The gastroprotective effect of C. barometz leaves against ethanol-induced gastric hemorrhagic abrasions in Sprague Dawley rats has been evaluated in terms of medicinal properties. Seven groups of rats (normal control and ulcerated control groups, omeprazole 20 mg/kg, 62.5, 125, 250, and 500 mg/kg of C. barometz correspondingly) were used in antiulcer experiment and pretreated with 10% Tween 20. After 1 hour, the normal group was orally administered 10% Tween 20, whereas absolute alcohol was fed orally to ulcerated control, omeprazole, and experimental groups. Gastric's homogenate were assessed for endogenous enzymes activities. Stomachs were examined macroscopically and histologically. Grossly, the data demonstrated a significant decrease in the ulcer area of rats pretreated with plant extract in a dose-dependent manner with respect to the ulcerated group. Homogenates of the gastric tissue exhibited significantly increased endogenous enzymes activities in rats pretreated with C. barometz extract associated with the ulcerated control group. Histology of rats pretreated with C. barometz extract group using hematoxylin and eosin staining exhibited a moderate-to-mild disruption of the surface epithelium with reduction in submucosal edema and leucocyte infiltration in a dose-dependent manner. In addition, it showed heat shock protein70 protein up-expression and BCL2-associated X protein downexpression. These outcomes might be attributed to the gastroprotective and antioxidative effects of the plant.

Matched MeSH terms: Plant Extracts/administration & dosage; Plant Extracts/isolation & purification; Plant Extracts/therapeutic use*
Fulltext Anti-ulcerogenic effect of methanolic extracts from Enicosanthellum pulchrum (King) Heusden against ethanol-induced acute gastric lesion in animal models

Nordin N, Salama SM, Golbabapour S, Hajrezaie M, Hassandarvish P, Kamalidehghan B, et al.

PLoS One, 2014;9(11):e111925.
PMID: 25379712 DOI: 10.1371/journal.pone.0111925

A natural source of medicine, Enicosanthellum pulchrum is a tropical plant which belongs to the family Annonaceae. In this study, methanol extract from the leaves and stems of this species was evaluated for its gastroprotective potential against mucosal lesions induced by ethanol in rats. Seven groups of rats were assigned, groups 1 and 2 were given Tween 20 (10% v/v) orally. Group 3 was administered omeprazole 20 mg/kg (10% Tween 20) whilst the remaining groups received the leaf and stem extracts at doses of 150 and 300 mg/kg, respectively. After an additional hour, the rats in groups 2-7 received ethanol (95% v/v; 8 mL/kg) orally while group 1 received Tween 20 (10% v/v) instead. Rats were sacrificed after 1 h and their stomachs subjected to further studies. Macroscopically and histologically, group 2 rats showed extremely severe disruption of the gastric mucosa compared to rats pre-treated with the E. pulchrum extracts based on the ulcer index, where remarkable protection was noticed. Meanwhile, a significant percentage of inhibition was shown with the stem extract at 62% (150 mg/kg) and 65% (300 mg/kg), whilst the percentage with the leaf extract at doses of 150 and 300 mg/kg was 63% and 75%, respectively. An increase in mucus content, nitric oxide, glutathione, prostaglandin E2, superoxide dismutase, protein and catalase, and a decrease in malondialdehyde level compared to group 2 were also obtained. Furthermore, immunohistochemical staining of groups 4-7 exhibited down-regulation of Bax and up-regulation of Hsp70 proteins. The methanol extract from the leaves and the stems showed notable gastroprotective potential against ethanol.

Matched MeSH terms: Plant Extracts/pharmacology*
Fulltext Efficacy of Boesenbergia rotunda Treatment against Thioacetamide-Induced Liver Cirrhosis in a Rat Model

Salama SM, Bilgen M, Al Rashdi AS, Abdulla MA

Evid Based Complement Alternat Med, 2012;2012:137083.
PMID: 22988470 DOI: 10.1155/2012/137083

Background. Experimental research in hepatology has focused on developing traditional medicines into potential pharmacological solutions aimed at protecting liver from cirrhosis. Along the same line, this study investigated the effects of ethanol-based extract from a traditional medicine plant Boesenbergia rotunda (BR) on liver cirrhosis. Methodology/Results. The BR extract was tested for toxicity on 3 groups of rats subjected to vehicle (10% Tween 20, 5 mL/kg) and 2g/kg and 5g/kg doses of the extract, respectively. Next, experiments were conducted on a rat model of cirrhosis induced by thioacetamide injection. The rats were divided into five groups and, respectively, administered orally with 10% Tween-20 (5 mL/kg) (normal control group), 10% Tween-20 (5 mL/kg) (cirrhosis control group), 50 mg/kg of silymarin (reference control group), and 250 mg/kg and 500 mg/kg of BR extract (experimental groups) daily for 8 weeks. The rats in normal group were intraperitoneally injected with sterile distilled water (1 mL/kg) 3 times/week, and those in the remaining groups were injected intraperitoneally with thioacetamide (200 mg/kg) thrice weekly. At the end of the 8 weeks, the animals were sacrificed and samples were collected for comprehensive histopathological, coagulation profile and biochemical evaluations. Also, the antioxidant activity of the BR extract was determined and compared with that of silymarin. Data from the acute toxicity tests showed that the extract was safe to use. Histological analysis of the livers of the rats in cirrhosis control group revealed uniform coarse granules on their surfaces, hepatocytic necrosis, and lymphocytes infiltration. But, the surfaces morphologically looked much smoother and the cell damage was much lesser in those livers from the normal control, silymarin and BR-treated groups. In the high-dose BR treatment group, the livers of the rats exhibited nearly normal looking lobular architecture, minimal inflammation, and minimal hepatocyte damage, the levels of the serum biomarkers and liver enzymes read nearly normal, and these results were all comparable to those observed or quantified from the normal and silymarin-treated groups. The BR extract had the antioxidant activity about half of what was recorded for silymarin. Conclusion. The progression of the liver cirrhosis can be intervened using the ethanol-based BR extract, and the liver's status quo of property, structure, and function can be preserved. This capability of the extract warrants further studies exploring the significance of its pharmacologic potential in successfully treating the liver cirrhosis in humans.

Matched MeSH terms: Plant Extracts
Fulltext The gastro protective effects of Cibotium barometz hair on ethanol-induced gastric ulcer in Sprague-Dawley rats

Al-Wajeeh NS, Hajerezaie M, Noor SM, Halabi MF, Al-Henhena N, Azizan AH, et al.

BMC Vet Res, 2017 Jan 19;13(1):27.
PMID: 28103938 DOI: 10.1186/s12917-017-0949-z

Cibotium barometz is a medical herb used traditionally in the Malaysian peninsula for several ailments, including gastric ulcer. The aim of this study was assessment the anti-ulcer effects of C. barometz hair on ethanol-induced stomach hemorrhagic abrasions in animals. Seven groups of Sprague Dawley (SD) rats were administered 10% Tween 20 in the normal control and ulcer control groups, and omeprazole 20 mg/kg and 62.5, 125, 250, and 500 mg/kg of C. barometz hair extract in the experimental groups. After 60 min, the normal control group of rats was orally administered 10% Tween 20, while absolute ethanol was orally administered to the groups of ulcer control, omeprazole and experimental groups. Stomachs of the rats were examined macroscopically and histologically. Homogenates of stomachs were used to evaluate endogenous antioxidant enzyme activities.

Matched MeSH terms: Plant Extracts/administration & dosage; Plant Extracts/pharmacology*; Plant Extracts/chemistry
Study of the Behaviors of Gunshot Residues from Spent Cartridges by Headspace Solid-Phase Microextraction-Gas Chromatographic Techniques

Chang KH, Yew CH, Abdullah AF

J Forensic Sci, 2015 Jul;60(4):869-77.
PMID: 25771708 DOI: 10.1111/1556-4029.12745

Gunshot residues, produced after shooting activity, have acquired their importance in analysis due to the notoriety of firearms-related crimes. In this study, solid-phase microextraction was performed to extract the headspace composition of spent cartridges using 85-μm polyacrylate fiber at 66°C for 21 min. Organic compounds, that is, naphthalene, 2,6-dinitrotoluene, 2,4-dinitrotoluene, diphenylamine, and dibutyl phthalate were detected and analyzed by gas chromatography-flame ionization detection technique. Evaluation of chromatograms for diphenylamine, dibutyl phthalate, and naphthalene indicates the period after a gunshot was discharged, whether it was 1 days, 2-4 days, <5 days, 10 days, 20 days, or more than 30 days ago. This study revealed the potential effects of environmental factors such as occasional wind blow and direct sunlight on the estimation of time after spent cartridges were discharged. In conclusion, we proposed reliable alternative in analyzing the headspace composition of spent cartridges in a simulated crime scene.

Matched MeSH terms: Plant Extracts
Fulltext The antinociceptive action of aqueous extract from Muntingia calabura leaves: the role of opioid receptors

Zakaria ZA, Mustapha S, Sulaiman MR, Mat Jais AM, Somchit MN, Abdullah FC

Med Princ Pract, 2007;16(2):130-6.
PMID: 17303949

The present study was carried out to investigate the antinociceptive activity of the aqueous extract of Muntingia calabura (MCAE) leaves and to determine the effect of temperature and the involvement of the opioid receptor on the said activity using the abdominal constriction test (ACT) and hot-plate test (HPT) in mice.

Matched MeSH terms: Plant Extracts/pharmacology*
Antinociceptive and anti-inflammatory properties of Corchorus capsularis leaves chloroform extract in experimental animal models

Zakaria ZA, Sulaiman MR, Gopalan HK, Abdul Ghani ZD, Raden Mohd Nor RN, Mat Jais AM, et al.

Yakugaku Zasshi, 2007 Feb;127(2):359-65.
PMID: 17268156

The antinociceptive and anti-inflammatory properties of Corchorus capsularis leaves chloroform extract were investigated in experimental animal models. The antinociceptive activity was measured using the writhing, hot plate and formalin tests, while the anti-inflammatory activity was measured using the carrageenan-induced paw edema test. The extract, obtained after 72 h soaking of the air-dried leaves in chloroform followed by in vacuo evaporation to dryness, was weighed and prepared by serial dilution in DMSO in the doses of 20, 100 and 200 mg/kg. The extract was administered (s.c.) 30 min prior to subjection to the respective assays. The extract was found to exhibit significant (p < 0.05) antinociceptive and anti-inflammatory activities. As a conclusion, the present study confirmed the traditional claims of using C. capsularis to treat various ailments related to inflammation and pain.

Matched MeSH terms: Plant Extracts/isolation & purification*; Plant Extracts/therapeutic use*
The antinociceptive activity of Muntingia calabura aqueous extract and the involvement of L-arginine/nitric oxide/cyclic guanosine monophosphate pathway in its observed activity in mice

Zakaria ZA, Sulaiman MR, Jais AM, Somchit MN, Jayaraman KV, Balakhrisnan G, et al.

Fundam Clin Pharmacol, 2006 Aug;20(4):365-72.
PMID: 16867020

The present study was carried out to investigate on the possible involvement of L-arginine/nitric oxide/cyclic guanosine monophosphate (L-arginine/NO/cGMP) pathway in the aqueous extract of Muntingia calabura (AEMC) leaves antinociception in mice assessed by abdominal constriction test. The AEMC, obtained by soaking the dried leaves in distilled water (DH(2)O) (1 : 2; w/v) for 24 h, was prepared in concentrations of 10%, 50% and 100% that were approximately equivalent to doses of 27, 135 and 270 mg/kg, and administered subcutaneously (s.c.) 5 min after pre-treatment (s.c.) of mice with DH(2)O, L-arginine (20 mg/kg), N(G)-monomethyl-L-arginine acetate (L-NMMA; 20 mg/kg), N(G)-nitro-L-arginine methyl esters (L-NAME; 20 mg/kg), methylene blue (MB) (20 mg/kg), respectively. The AEMC was found to exhibit a concentration-dependent antinociception after pre-challenge with DH(2)O. Interestingly, pre-treatment with L-arginine was found to block significantly (P < 0.05) the AEMC antinociception but only at the highest concentration (100%) of AEMC used. On the other hand, pre-treatment with L-NAME was found to significantly (P < 0.05) enhance the low concentration but inhibit the high concentration AEMC antinociception. MB was found to significantly (P < 0.05) enhance AEMC antinociception at all concentrations used. Except for the higher concentration of AEMC used, co-treatment with L-NAME was found to insignificantly and significantly (P < 0.05) reverse the L-arginine effect when given alone or with low concentration AEMC, respectively. In addition, co-treatment with MB significantly (P < 0.05) reversed the L-arginine effect when given alone or with 10% concentration AEMC but failed to affect the activity of the rest of concentrations used. As a conclusion, this study has demonstrated the involvement of L-arginine/NO/cGMP pathway in AEMC antinociception.

Matched MeSH terms: Plant Extracts/pharmacology; Plant Extracts/therapeutic use
Antinociceptive and anti-inflammatory activities of Dicranopteris linearis leaves chloroform extract in experimental animals

Zakaria ZA, Abdul Ghani ZD, Raden Mohd Nor RN, Gopalan HK, Sulaiman MR, Abdullah FC

Yakugaku Zasshi, 2006 Nov;126(11):1197-203.
PMID: 17077622

The present study was carried out to establish the antinociceptive and anti-inflammatory properties of Dicranopteris linearis leaves chloroform extract in experimental animals. The antinociceptive activity was measured using the abdominal constriction, formalin and hot plate tests, while the anti-inflammatory activity was measured using the carrageenan-induced paw edema. The extract, obtained after 72 h soaking of the air-dried leaves in chloroform followed by evaporation under vacuo (40 degrees C) to dryness, was dissolved in dimethyl sulfoxide to the doses of 20, 100 and 200 mg/kg and administered subcutaneously 30 min prior to subjection to the above mentioned assays. The extract, at all doses used, was found to exhibit significant (p<0.05) antinociceptive activity in a dose-dependent manner. However, the significant (p<0.05) anti-inflammatory activity observed occur in a dose-independent manner. As a conclusion, the chloroform extract of D. linearis possesses antinociceptive and anti-inflammatory activity and thus justify its traditional uses by the Malays to treat various ailments.

Matched MeSH terms: Plant Extracts/isolation & purification; Plant Extracts/therapeutic use
Fulltext Antioxidant and hepatoprotective effects of Murdannia bracteata methanol extract

Yam MF, Ang LF, Lim CP, Ameer OZ, Salman IM, Ahmad M, et al.

J Acupunct Meridian Stud, 2010 Sep;3(3):197-202.
PMID: 20869021 DOI: 10.1016/S2005-2901(10)60036-2

Murdannia bracteata (C. B. Clarke) is a local plant that is widely used in Malaysia as a traditional remedy for various diseases of the kidney and liver, including inflammation and cancer. In the present study, we investigated the antioxidant and hepatoprotective activities of M. bracteata methanol extract (MB). 2,2'-diphenyl-1-picrylhydrazyl radical scavenging activity, lipid peroxidation inhibition and trolox equivalent antioxidant capacity of MB were determined. The hepatoprotective activity of MB was studied using a CCl(4)-induced liver toxicity model in rats. The hepatoprotective effect was assessed by monitoring the plasma malondialdehyde level and serum alanine transaminase and aspartate transaminase activities. Histopathological changes of hepatic tissue were also investigated. The results indicated that MB possessed potential antioxidant, lipid peroxidation inhibition and free radical scavenging activities. Pretreatment of rats with MB (500 mg/kg and 1000 mg/kg per os) before induction of CCl(4)-induced hepatotoxicity showed a dose-dependent reduction in the necrotic changes in hepatic tissue. The increases in plasma malondialdehyde level, serum alanine transaminase and aspartate transaminase activities were also significantly inhibited by MB. The total phenolic content of MB determined using Folin-Ciocalteu assay was found to be 10%. The results of the present study indicated that the hepatoprotective effect of MB is most likely due to its antioxidant and free radical scavenging properties.

Matched MeSH terms: Plant Extracts/pharmacology*
Effects of asiatic acid on passive and active avoidance task in male Spraque-Dawley rats

Nasir MN, Habsah M, Zamzuri I, Rammes G, Hasnan J, Abdullah J

J Ethnopharmacol, 2011 Mar 24;134(2):203-9.
PMID: 21167268 DOI: 10.1016/j.jep.2010.12.010

Centella asiatica has a reputation to restore declining cognitive function in traditional medicine. To date, only a few compounds that show enhancing learning and memory properties are available. Therefore, the present study investigates the effects of for acute administration of asiatic acid (A-A) isolated from Centella asiatica administration on memory and learning in male Spraque-Dawley rats.

Matched MeSH terms: Plant Extracts/pharmacology*
Acute toxicity study of the standardized methanolic extract of Mitragyna speciosa Korth in rodent

Harizal SN, Mansor SM, Hasnan J, Tharakan JK, Abdullah J

J Ethnopharmacol, 2010 Sep 15;131(2):404-9.
PMID: 20643198 DOI: 10.1016/j.jep.2010.07.013

ETHNOPHARMACOLOGICAL RELEVANCE: Mitragyna speciosa Korth (ketum) is widely used in Malaysia as a medicinal agent for treating diarrhea, worm infestations and also acts as an analgesic and antipyretic.
AIM: The aim of the study is to determine the acute toxicity of Mitragyna speciosa Korth standardized methanol extract in vivo in 4-weeks-old Sprague-Dawley rats.
METHODOLOGY: Rats were orally administrated single dose of 100, 500 and 1000 mg/kg Mitragyna speciosa Korth standardized methanol extract and the control group received 430 mg/kg of morphine orally. There were 10 rats in each group. All animals were sacrificed after 14 days of treatment. Eight parameters were tested: cage side observation, body weight measurement, food and water consumption, blood pressure, absolute and relative organ weight, hematology, biochemical analysis and histopathology, to look for evidence of toxicity.
RESULT: No mortality was noted after 14 days of treatment. In general, behavior, food and water consumption, hematological studies and organ weights showed no significant changes. The standardized methanol extraction of Mitragyna speciosa Korth increased rat blood pressure (systolic: 147.4+/-1.01, 131.64+/-4.94 and 137.8+/-4.46) after an hour of 100, 500 and 1000 mg/kg doses, respectively. Biochemical studies showed significant elevation of ALT, AST, albumin, triglycerides, cholesterol and albumin (p>0.05), at all levels of doses. But, nephrotoxicity evidenced by elevated creatinine was seen only at a dose of 1000 mg/kg. Histological examination showed congestion of sinusoids, hemorrhage hepatocytes, fatty change, centrilobular necrosis and increased number of Kuppfer cells in the liver of all Mitragyna speciosa Korth standardized methanol extract treated groups.
CONCLUSION: Oral administration of standardized methanolic extraction of Mitragyna speciosa Korth resulted in increasing rat blood pressure after an hour of drug administration. The highest dose of extract also induced acute severe hepatotoxicity and mild nephrotoxicity. However, Mitragyna speciosa Korth shows no effects on body weight, food and water consumption, absolute and relative organ weight and also hematology parameters.

Matched MeSH terms: Plant Extracts/toxicity*
Clausenidin Induces Caspase 8-Dependent Apoptosis and Suppresses Production of VEGF in Liver Cancer Cells

Waziri PM, Abdullah R, Rosli R, Omar AR, Abdul AB, Kassim NK, et al.

Asian Pac J Cancer Prev, 2018 Apr 25;19(4):917-922.
PMID: 29693341

Clausena excavata Burm f. is used by traditional healers to treat cancer patients in South East Asia. The use of the
plant and its compounds is based on Asian folklore with little or no scientific evidence supporting the therapeutic efficacy
The current study aimed to determine the effect of pure clausenidin isolated from C. excavata on caspase-8-induced cell
death as well as angiogenesis in the HepG2 hepatocellular carcinoma cell line. Caspase-8 and extrinsic death receptor
protein expression was determined using spectrophotometry and protein profile arrays, respectively. Ultrastructural
analysis of clausenidin-treated cells was conducted using transmission electron microscopy. In addition, anti-angiogenic
effects of clausenidin were investigated by Western blot analysis. Clausenidin significantly (p<0.05) increased the
activity of caspase-8 and expression of protein components of the death inducing signaling complex (DISC) in HepG2
cells. Ultrastructural analysis of the clausenidin-treated HepG2 cells revealed morphological abnormalities typical of
apoptosis. Furthermore, clausenidin significantly (p<0.05) decreased the expression of vascular endothelial growth
factor (VEGF). Therefore, clausenidin is a potential anti-angiogenic agent which may induce apoptosis of hepatocellular
carcinoma cells.

Matched MeSH terms: Plant Extracts/pharmacology*
Fulltext Differential expression of entorhinal cortex and hippocampal subfields α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptors enhanced learning and memory of rats following administration of Centella asiatica

Wong JH, Muthuraju S, Reza F, Senik MH, Zhang J, Mohd Yusuf Yeo NAB, et al.

Biomed Pharmacother, 2019 Feb;110:168-180.
PMID: 30469081 DOI: 10.1016/j.biopha.2018.11.044

Centella asiatica (CA) is a widely used traditional herb, notably for its cognitive enhancing effect and potential to increase synaptogenesis. The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) and N-methyl-D-aspartate receptors (NMDARs) mediate fast excitatory neurotransmission with key roles in long-term potentiation which is believed to be the cellular mechanism of learning and memory. Improved learning and memory can be an indication to the surface expression level of these receptors. Our previous study demonstrated that administration of CA extract improved learning and memory and enhanced expression of AMPAR GluA1 subunit while exerting no significant effects on GABAA receptors of the hippocampus in rats. Hence, to further elucidate the effects of CA, this study investigated the effects of CA extract in recognition memory and spatial memory, and its effects on AMPAR GluA1 and GluA2 subunit and NMDAR GluN2 A and GluN2B subunit expression in the entorhinal cortex (EC) and hippocampal subfields CA1 and CA3. The animals were administered with saline, 100 mg/kg, 300 mg/kg, and 600 mg/kg of CA extract through oral gavage for 14 days, followed by behavioural analysis through Open Field Test (OFT), Novel Object Recognition Task (NORT), and Morris Water Maze (MWM) and lastly morphological and immunohistochemical analysis of the surface expression of AMPAR and NMDAR subunits were performed. The results showed that 14 days of administration of 600 mg/kg of CA extract significantly improved memory assessed through NORT while 300 mg/kg of CA extract significantly improved memory of the animals assessed through MWM. Immunohistochemical analysis revealed differential modulation effects on the expressions of receptor subunits across CA1, CA3 and EC. The CA extract at the highest dose (600 mg/kg) significantly enhanced the expression of AMPAR subunit GluA1 and GluA2 in CA1, CA3 and EC, and NMDAR subunit GluN2B in CA1 and CA3 compared to control. At 300 mg/kg, CA significantly increased expression of AMPAR GluA1 in CA1 and EC, and GluA2 in CA1, CA3 and EC while 100 mg/kg of CA significantly increased expression of only AMPAR subunit GluA2 in CA3 and EC. Expression of NMDAR subunit GluN2 A was significantly reduced in the CA3 (at 100, 300, and 600 mg/kg) while no significant changes of subunit expression was observed in CA1 and EC compared to control. The results suggest that the enhanced learning and memory observed in animals administered with CA was mainly mediated through increased expression of AMPAR GluA1 and GluA2 subunits and differential expression of NMDAR GluN2 A and GluN2B subunits in the hippocampal subfields and EC. With these findings, the study revealed a new aspect of cognitive enhancing effect of CA and its therapeutic potentials through modulating receptor subunit expression.

Matched MeSH terms: Plant Extracts/isolation & purification; Plant Extracts/pharmacology*
Fulltext Modulation of Hydrogen Peroxide-Induced Oxidative Stress in Human Neuronal Cells by Thymoquinone-Rich Fraction and Thymoquinone via Transcriptomic Regulation of Antioxidant and Apoptotic Signaling Genes

Ismail N, Ismail M, Azmi NH, Abu Bakar MF, Basri H, Abdullah MA

Oxid Med Cell Longev, 2016;2016:2528935.
PMID: 26823946 DOI: 10.1155/2016/2528935

Nigella sativa Linn. (N. sativa) and its bioactive constituent Thymoquinone (TQ) have demonstrated numerous pharmacological attributes. In the present study, the neuroprotective properties of Thymoquinone-rich fraction (TQRF) and TQ against hydrogen peroxide- (H2O2-) induced neurotoxicity in differentiated human SH-SY5Y cells were investigated. TQRF was extracted using supercritical fluid extraction while TQ was acquired commercially, and their effects on H2O2 were evaluated using cell viability assay, reactive oxygen species (ROS) assay, morphological observation, and multiplex gene expression. Both TQRF and TQ protected the cells against H2O2 by preserving the mitochondrial metabolic enzymes, reducing intracellular ROS levels, preserving morphological architecture, and modulating the expression of genes related to antioxidants (SOD1, SOD2, and catalase) and signaling genes (p53, AKT1, ERK1/2, p38 MAPK, JNK, and NF-κβ). In conclusion, the enhanced efficacy of TQRF over TQ was likely due to the synergism of multiple constituents in TQRF. The efficacy of TQRF was better than that of TQ alone when equal concentrations of TQ in TQRF were compared. In addition, TQRF also showed comparable effects to TQ when the same concentrations were tested. These findings provide further support for the use of TQRF as an alternative to combat oxidative stress insults in neurodegenerative diseases.

Matched MeSH terms: Plant Extracts/chemistry
Fulltext Mikania micrantha Extract Inhibits HMG-CoA Reductase and ACAT2 and Ameliorates Hypercholesterolemia and Lipid Peroxidation in High Cholesterol-Fed Rats

Ibrahim A, Shafie NH, Mohd Esa N, Shafie SR, Bahari H, Abdullah MA

Nutrients, 2020 Oct 09;12(10).
PMID: 33050310 DOI: 10.3390/nu12103077

The present study aimed to determine the effect of an ethyl acetate extract of Mikania micrantha stems (EAMMS) in hypercholesterolemia-induced rats. Rats were divided into a normal group (NC) and hypercholesterolemia induced groups: hypercholesterolemia control group (PC), simvastatin group (SV) (10 mg/kg) and EAMMS extract groups at different dosages of 50, 100 and 200 mg/kg, respectively. Blood serum and tissues were collected for haematological, biochemical, histopathological, and enzyme analysis. Total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), aspartate aminotransferase (AST), alanine aminotransferase (ALT), urea, creatinine, malondialdehyde (MDA) level, as well as enzymes of HMG-CoA reductase (HMGCR) and acetyl-CoA acetyltransferase 2 (ACAT2), were measured. Feeding rats with high cholesterol diet for eight weeks resulted in a significantly (p < 0.05) increased of TC, TG, LDL-C, AST, ALT and MDA levels. Meanwhile, the administration of EAMMS extract (50, 100 and 200 mg/kg) and simvastatin (10 mg/kg) significantly reduced (p < 0.05) the levels of TC, TG, LDL-C and MDA compared to rats in the PC group. Furthermore, all EAMMS and SV-treated groups showed a higher HDL-C level compared to both NC and PC groups. No significant difference was found in the level of ALT, AST, urea and creatinine between the different dosages in EAMMS extracts. Treatment with EAMMS also exhibited the highest inhibition activity of enzyme HMGCR and ACAT2 as compared to the control group. From the histopathological examination, liver tissues in the PC group showed severe steatosis than those fed with EAMMS and normal diet. Treatment with EAMMS extract ameliorated and reduced the pathological changes in the liver. No morphological changes showed in the kidney structure of both control and treated groups. In conclusion, these findings demonstrated that EAMMS extract has anti-hypercholesterolemia properties and could be used as an alternative treatment for this disorder.

Matched MeSH terms: Plant Extracts/administration & dosage*; Plant Extracts/isolation & purification; Plant Extracts/pharmacology*

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