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Antioxidant and Wound Healing Activity of Polyherbal Fractions of Clinacanthus nutans and Elephantopus scaber

Aslam MS, Ahmad MS, Mamat AS, Ahmad MZ, Salam F

Evid Based Complement Alternat Med, 2016;2016:4685246.
PMID: 27528881 DOI: 10.1155/2016/4685246

Elephantopus scaber and Clinacanthus nutans are traditionally used as wound healing herb. The objective of the present study is to develop a new polyherbal formulation, by comparison, the herbal combination of Elephantopus scaber and Clinacanthus nutans as an in vitro antioxidant activity with their individual herbal activity followed by fractionation of polyherbal formulation for in vivo wound healing activities and identification of bioactive compounds from their active fractions. Antioxidant activity was performed in vitro by DPPH scavenging antioxidant activity followed by in vivo wound healing activities using excision wound model, incision wound model, and burn wound model. Toxicity of the fractions of the polyherbal formulation was performed by a dermal toxicity test. The result showed that Elephantopus scaber crude extract on the basis of EC50 performs a much faster action (15.67 μg/mL) but with less % inhibition (87.66%) as compared to the combination of the new polyherbal formulation of crude extract (30 μg/mL). The polyherbal formulation has the highest % inhibition (89.49%) at the same dose as compared to Elephantopus scaber (87.66%). In comparison among all crude and fractions of new polyherbal formulation, it was found that the ethyl acetate fraction of polyherbal formulation has the fastest activity (EC50 14.83 μg/mL) with % inhibition (89.28%). Furthermore, during evaluation of wound contraction on excision and incision wound model, ethyl acetate fraction possesses the highest activity with (P < 0.001) and (P < 0.0001), respectively. During burn wound model, aqueous fraction (P < 0.001) possesses the highest activity followed by an ethyl acetate fraction (P < 0.0001). LC-MS analysis discovered the presence of several flavonoid-based compounds that work synergistically with sesquiterpene lactone and other bioactive compounds. In conclusion, flavonoid increases the antioxidant activity that surges the rate of wound contraction and works synergistically with other bioactive compounds.
Fulltext Antioxidative Effects of Germinated Brown Rice-Derived Extracts on H2O2-Induced Oxidative Stress in HepG2 Cells

Md Zamri ND, Imam MU, Abd Ghafar SA, Ismail M

Evid Based Complement Alternat Med, 2014;2014:371907.
PMID: 25431609 DOI: 10.1155/2014/371907

The antioxidant properties of germinated brown rice (GBR) are likely mediated by multiple bioactives. To test this hypothesis, HepG2 cells pretreated with GBR extracts, rich in acylated steryl glycoside (ASG), gamma amino butyric acid GABA), phenolics or oryzanol, were incubated with hydrogen peroxide (H2O2) and their hydroxyl radical (OH(•)) scavenging capacities and thiobarbituric acid-reactive substances (TBARS) generation were evaluated. Results showed that GBR-extracts increased OH(•) scavenging activities in both cell-free medium and posttreatment culture media, suggesting that the extracts were both direct- and indirect-acting against OH(•). The levels of TBARS in the culture medium after treatment were also reduced by all the extracts. In addition, H2O2 produced transcriptional changes in p53, JNK, p38 MAPK, AKT, BAX, and CDK4 that were inclined towards apoptosis, while GBR-extracts showed some transcriptional changes (upregulation of BAX and p53) that suggested an inclination for apoptosis although other changes (upregulation of antioxidant genes, AKT, JNK, and p38 MAPK) suggested that GBR-extracts favored survival of the HepG2 cells. Our findings show that GBR bioactive-rich extracts reduce oxidative stress through improvement in antioxidant capacity, partly mediated through transcriptional regulation of antioxidant and prosurvival genes.
Fulltext Antioxidative and cardioprotective properties of anthocyanins from defatted dabai extracts

Khoo HE, Azlan A, Nurulhuda MH, Ismail A, Abas F, Hamid M, et al.

Evid Based Complement Alternat Med, 2013;2013:434057.
PMID: 24368926 DOI: 10.1155/2013/434057

This study aimed to determine anthocyanins and their antioxidative and cardioprotective properties in defatted dabai parts. Anthocyanins in crude extracts and extract fractions of defatted dabai peel and pericarp were quantified using UHPLC, while their antioxidant capacity and oxidative stress inhibition ability were evaluated by using DPPH and CUPRAC assays as well as linoleic acid oxidation system, hemoglobin oxidation, and PARP-1 inhibition ELISA. Cardioprotective effect of the defatted dabai peel extract was evaluated using hypercholesterolemic-induced New Zealand white rabbits. Six anthocyanins were detected in the defatted dabai peel, with the highest antioxidant capacities and oxidative stress inhibition effect compared to the other part. The defatted dabai peel extract has also inhibited lipid peroxidation (plasma MDA) and elevated cellular antioxidant enzymes (SOD and GPx) in the tested animal model. Major anthocyanin (cyanidin-3-glucoside) and other anthocyanins (pelargonidin-3-glucoside, malvidin-3-glucoside, cyanidin-3-galactoside, cyanidin-3-arabinoside, and peonidin-3-glucoside) detected in the defatted dabai peel are potential future nutraceuticals with promising medicinal properties.
Fulltext Antiproliferative and Proapoptotic Effects of Labisia pumila Ethanol Extract and Its Active Fraction in Human Melanoma HM3KO Cells

Lope Pihie AH, Zakaria ZA, Othman F

Evid Based Complement Alternat Med, 2012;2012:123470.
PMID: 22474490 DOI: 10.1155/2012/123470

The present study was to determine the anticancer potential of Labisia pumila in in vitro models. Results from the study revealed that ethanol extract of L. pumila was more cytotoxic against HM3KO cells while having reduced effects on nonmalignant cells as compared to aqueous and hexane extracts. Thus, ethanol extract was selected to be further separated by using the bioassay-guided fractionation method to give an active fraction, SF2Lp. Results obtained from the flow cytometry analysis showed that SF2Lp was able to arrest the HM3KO cell cycle at the G1 phase, while morphological findings from AO-EB nuclear staining assays along with the Apoptotic Index confirmed the induction of apoptosis by SF2Lp in HM3KO cells. Results from the mechanistic study further revealed that SF2Lp treatment was able to concurrently increase the expression level of p53 and pro-apoptotic protein Bax and also reduce the expression level of anti-apoptotic protein BCl-2 in HM3KO cells, directly contributing to the increase in Bax/Bcl-2 ratio. These findings, therefore, suggested that L. pumila was able to inhibit HM3KO cell growth possibly by arresting the cell cycle at G1 phase and inducing apoptosis in HM3KO cells via the up- and down-regulation of Bax/Bcl-2 protein, mediated through a p53-dependent pathway.
Fulltext Antiulcer Effect of Honey in Nonsteroidal Anti-Inflammatory Drugs Induced Gastric Ulcer Model in Rats: A Systematic Review

Fazalda A, Quraisiah A, Nur Azlina MF

Evid Based Complement Alternat Med, 2018;2018:7515692.
PMID: 30105063 DOI: 10.1155/2018/7515692

Background: Peptic ulcer is a basic term for ulcers on the lower oesophagus, stomach, or jejunum. The specific term for ulcer in the stomach is gastric ulcer. The extensive use of honey around the globe helps researchers to study the usefulness of honey. Many studies had already been conducted and proved the effectiveness of honey in treating gastric ulcer.
Methods: A systematic review of the literature was conducted to identify relevant studies on honey used as an alternative treatment of gastric ulcer cause by NSAIDs. A comprehensive search was conducted in Medline, SCOPUS, and Ebscohost. The main criteria used were articles published in English and using NSAIDs-induced gastric ulcer in rat's model and those reporting the effectiveness of honey.
Results: Articles published between 2001 and 2014 were identified to be relevant in studies related to the inclusion criteria. The literature search found 30 potential and closely related articles in this review, but only 5 articles were taken which meet the criteria needed to be fulfilled.
Conclusions: All studies in this review reported the efficacy of honey for gastric ulcer based on its antioxidant and cytoprotective activities. Most of the studies conducted used different types of honey at various doses on rats. Future studies should be conducted to identify the appropriate dose for humans to achieve similar gastroprotective effects.
Fulltext Apoptosis Effect of Girinimbine Isolated from Murraya koenigii on Lung Cancer Cells In Vitro

Mohan S, Abdelwahab SI, Cheah SC, Sukari MA, Syam S, Shamsuddin N, et al.

Evid Based Complement Alternat Med, 2013;2013:689865.
PMID: 23573145 DOI: 10.1155/2013/689865

Murraya koenigii Spreng has been traditionally claimed as a remedy for cancer. The current study investigated the anticancer effects of girinimbine, a carbazole alkaloid isolated from Murraya koenigii Spreng, on A549 lung cancer cells in relation to apoptotic mechanistic pathway. Girinimbine was isolated from Murraya koenigii Spreng. The antiproliferative activity was assayed using MTT and the apoptosis detection was done by annexin V and lysosomal stability assays. Multiparameter cytotoxicity assays were performed to investigate the change in mitochondrial membrane potential and cytochrome c translocation. ROS, caspase, and human apoptosis proteome profiler assays were done to investigate the apoptotic mechanism of cell death. The MTT assay revealed that the girinimbine induces cell death with an IC50 of 19.01 μ M. A significant induction of early phase of apoptosis was shown by annexin V and lysosomal stability assays. After 24 h treatment with 19.01 μ M of girinimbine, decrease in the nuclear area and increase in mitochondrial membrane potential and plasma membrane permeability were readily visible. Moreover the translocation of cytochrome c also was observed. Girinimbine mediates its antiproliferative and apoptotic effects through up- and downregulation of apoptotic and antiapoptotic proteins. There was a significant involvement of both intrinsic and extrinsic pathways. Moreover, the upregulation of p53 as well as the cell proliferation repressor proteins, p27 and p21, and the significant role of insulin/IGF-1 signaling were also identified. Moreover the caspases 3 and 8 were found to be significantly activated. Our results taken together indicated that girinimbine may be a potential agent for anticancer drug development.
Fulltext Application of Antrodia camphorata Promotes Rat's Wound Healing In Vivo and Facilitates Fibroblast Cell Proliferation In Vitro

Amin ZA, Ali HM, Alshawsh MA, Darvish PH, Abdulla MA

Evid Based Complement Alternat Med, 2015;2015:317693.
PMID: 26557855 DOI: 10.1155/2015/317693

Antrodia camphorata is a parasitic fungus from Taiwan, it has been documented to possess a variety of pharmacological and biological activities. The present study was undertaken to evaluate the potential of Antrodia camphorata ethanol extract to accelerate the rate of wound healing closure and histology of wound area in experimental rats. The safety of Antrodia camphorata was determined in vivo by the acute toxicity test and in vitro by fibroblast cell proliferation assay. The scratch assay was used to evaluate the in vitro wound healing in fibroblast cells and the excision model of wound healing was tested in vivo using four groups of adult Sprague Dawley rats. Our results showed that wound treated with Antrodia camphorata extract and intrasite gel significantly accelerates the rate of wound healing closure than those treated with the vehicle. Wounds dressed with Antrodia camphorata extract showed remarkably less scar width at wound closure and granulation tissue contained less inflammatory cell and more fibroblast compared to wounds treated with the vehicle. Masson's trichrom stain showed granulation tissue containing more collagen and less inflammatory cell in Antrodia camphorata treated wounds. In conclusion, Antrodia camphorata extract significantly enhanced the rate of the wound enclosure in rats and promotes the in vitro healing through fibroblast cell proliferation.
Fulltext Aqueous Extract of Phyllanthus niruri Leaves Displays In Vitro Antioxidant Activity and Prevents the Elevation of Oxidative Stress in the Kidney of Streptozotocin-Induced Diabetic Male Rats

Giribabu N, Rao PV, Kumar KP, Muniandy S, Swapna Rekha S, Salleh N

Evid Based Complement Alternat Med, 2014;2014:834815.
PMID: 24991228 DOI: 10.1155/2014/834815

P. niruri has been reported to possess antidiabetic and kidney protective effects. In the present study, the phytochemical constituents and in vitro antioxidant activity of P. niruri leaf aqueous extract were investigated together with its effect on oxidative stress and antioxidant enzymes levels in diabetic rat kidney. Results. Treatment of diabetic male rats with P. niruri leaf aqueous extract (200 and 400 mg/kg) for 28 consecutive days prevents the increase in the amount of lipid peroxidation (LPO) product, malondialdehyde (MDA), and the diminution of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activity levels in the kidney of diabetic rats. The amount of LPO showed strong negative correlation with SOD, CAT, and GPx activity levels. P. niruri leaf aqueous extract exhibits in vitro antioxidant activity with IC50 slightly lower than ascorbic acid. Phytochemical screening of plant extract indicates the presence of polyphenols. Conclusion. P. niruri leaf extract protects the kidney from oxidative stress induced by diabetes.
Fulltext Assessment of Antifungal Activity of Bakuchiol on Oral-Associated Candida spp

Nordin MA, Abdul Razak F, Himratul-Aznita WH

Evid Based Complement Alternat Med, 2015;2015:918624.
PMID: 26633986 DOI: 10.1155/2015/918624

Bakuchiol is an active component of Psoralea glandulosa and Psoralea corylifolia, used in traditional Chinese medicine. The study aimed at investigating the antifungal activity of bakuchiol on planktonic and biofilm forms of orally associated Candida species. The antifungal susceptibility testing was determined by the broth micro dilution technique. Growth kinetics and cell surface hydrophobicity (CSH) of Candida were measured to assess the inhibitory effect of bakuchiol on Candida planktonic cells. Biofilm biomass and cellular metabolic activity were quantitatively estimated by the crystal violet (CV) and the 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino)carbonyl]-2H-tetrazolium hydroxide (XTT) assays. All Candida strains have been shown to be susceptible to bakuchiol with the MIC ranges from 12.5 to 100 μg/mL. Significant decrease in specific growth rates and viable counts demonstrates the inhibitory effect of bakuchiol on Candida planktonic cells. A brief exposure to bakuchiol also reduced CSH of Candida (P < 0.05), indicating altered surface properties of yeast cells towards hydrophobic interfaces. Biofilm biomass and cell metabolic activity were mostly decreased, except for C. glabrata (P = 0.29). The antifungal properties of bakuchiol on Candida species in this in vitro study may give insights into the application in therapeutic strategy against Candida infections.
Fulltext Assessment of Toxicity and Beneficiary Effects of Garcinia pedunculata on the Hematological, Biochemical, and Histological Homeostasis in Rats

Paul S, Ali MY, Rumpa NE, Tanvir EM, Hossen MS, Saha M, et al.

Evid Based Complement Alternat Med, 2017;2017:4686104.
PMID: 28243309 DOI: 10.1155/2017/4686104

This study was undertaken to investigate the toxicological profile of a methanolic extract of Garcinia pedunculata fruit in rats by conducting hematological, biochemical, and histopathological examinations. Long Evans rats were divided into four groups, each with 6 animals, and were treated with three oral doses (250, 500, and 1000 mg/kg) once daily for 21 days. The extract did not cause significant changes in body and relative organ weight, percent water content, or hematological parameters at any administered doses. However, a significant dose-dependent positive effect in serum lipid profile and all atherogenic indices including the cardiac risk ratio, Castelli's risk index-2, and the atherogenic coefficient were observed. Significant increases in the levels of iron and decreases in serum alkaline phosphatase, alanine transaminase, and lactate dehydrogenase activities and the levels of serum glucose were noted when the extract was administered at the highest dose (1000 mg/kg). Histopathological examination of the target tissues further confirmed that the extract was safe and had no observed toxicological features. Our study indicates that G. pedunculata fruit is nontoxic, has the potential to be effective against atherosclerosis, and may be used as a hepatoprotectant. The fruit extract is also beneficial to those with iron deficiency and hyperglycemia.
Attenuation of Thrombosis by Crude Rice (Oryza sativa) Bran Policosanol Extract: Ex Vivo Platelet Aggregation and Serum Levels of Arachidonic Acid Metabolites

Wong WT, Ismail M, Tohit ER, Abdullah R, Zhang YD

Evid Based Complement Alternat Med, 2016;2016:7343942.
PMID: 27800004

Background. Vascular occlusion or thrombosis was often attributed to uncontrolled platelet activation. Influence of sugarcane policosanol extract on platelet was reported but little was known of rice bran policosanol, particularly its mechanisms of actions on platelet activities. Objective. Antiplatelet mechanisms of rice bran policosanol extract (RBE) were studied using hyperlipidemic Sprague Dawley rats. Ex vivo platelet aggregation, platelet count (PC), bleeding time (BT), and coagulation time were assayed. Serum eicosanoids and other aggregation-related metabolites levels were quantified. Design. Rats were divided into 6 groups for comparisons (vehicle control Tween 20/H2O, high dose policosanol 500 mg/kg, middle dose policosanol 250 mg/kg, low dose policosanol 100 mg/kg, and positive control aspirin 30 mg/kg). Results. Low dose 100 mg/kg of RBE inhibited aggregation by 42.32 ± 4.31% and this was comparable with the effect of 30 mg/kg aspirin, 43.91 ± 5.27%. Results showed that there were no significant differences in PC, BT, and coagulation time among various groups after RBE treatment. Serum thromboxane A2 was attenuated while prostacyclin level increased upon RBE treatment. Conclusions. RBE reduced ex vivo ADP-induced platelet aggregation without giving adverse effects. No changes in full blood count suggested that rice bran policosanol did not disturb biological blood cell production and destruction yet it reduced aggregation through different mechanisms.
Fulltext Autonomic Nervous System Mediates the Hypotensive Effects of Aqueous and Residual Methanolic Extracts of Syzygium polyanthum (Wight) Walp. var. polyanthum Leaves in Anaesthetized Rats

Ismail A, Mohamed M, Sulaiman SA, Wan Ahmad WA

Evid Based Complement Alternat Med, 2013;2013:716532.
PMID: 24454508 DOI: 10.1155/2013/716532

Syzygium polyanthum (Wight) Walp. var. polyanthum leaves are consumed as a traditional Malay treatment of hypertension. This study investigates hypotensive potential of aqueous (AESP) and residual methanolic (met-AESP) extracts of S. polyanthum leaves and possible involvement of autonomic receptors. AESP and met-AESP (20 to 100 mg/kg) were intravenously administered into anaesthetized Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats. Blood pressure and heart were monitored for 20 min. AESP and met-AESP induced significant dose-dependent hypotension, but only 100 mg/kg AESP caused mild bradycardia (n = 5). AESP-induced hypotension was more potent than that of met-AESP in WKY. AESP has a faster onset time than that of met-AESP in both WKY and SHR. However, met-AESP-induced hypotension was more sustained than that of AESP in SHR. Blockages of autonomic ganglion and α -adrenergic receptors using hexamethonium and phentolamine (n = 5 for each group) partially attenuated AESP-induced hypotension, suggesting involvement of α -adrenergic receptors. Blockages of autonomic ganglion, β -adrenergic, cholinergic receptors, and nitric oxide production using hexamethonium, propranolol, atropine, and N- ω -nitro-l arginine methyl ester (L-NAME) (n = 5 for each group) partially attenuated met-AESP-induced hypotension, suggesting involvement of β -adrenergic and cholinergic receptors via nitric oxide production.
Fulltext Behavioral and Histopathological Study of Changes in Spinal Cord Injured Rats Supplemented with Spirulina platensis

Aziz I, Che Ramli MD, Mohd Zain NS, Sanusi J

Evid Based Complement Alternat Med, 2014;2014:871657.
PMID: 25152764 DOI: 10.1155/2014/871657

Spinal cord injury (SCI) is a devastating disease that leads to permanent disability and causes great suffering. The resulting neurological dysfunction and paralysis is proportional to the severity of the trauma itself. Spirulina is widely used as a nutritional supplement due to its high protein and antioxidant content. In the present study, the protective effect of the Spirulina treatment on locomotor function and morphological damage after SCI was investigated. Seventy Sprague-Dawley (SD) rats were divided into three groups: Sham (laminectomy alone), Control (laminectomy with SCI), and Experimental (laminectomy with SCI +180 mg/kg per day Spirulina platensis). A laminectomy was performed at T12 and an Inox No.2 modified forceps was used to perform a partial crush injury on the spinal cord. The rats were then perfused at 3, 7, 14, 21, and 28 days after injury for morphological investigations. The injured rat spinal cord indicated a presence of hemorrhage, cavity, and necrosis. Pretreatment with Spirulina significantly improved the locomotor function and showed a significant reduction on the histological changes. The experimental results observed in this study suggest that treatment with Spirulina platensis possesses potential benefits in improving hind limb locomotor function and reducing morphological damage to the spinal cord.
Fulltext Beta-Glucan-Rich Extract from Pleurotus sajor-caju (Fr.) Singer Prevents Obesity and Oxidative Stress in C57BL/6J Mice Fed on a High-Fat Diet

Kanagasabapathy G, Malek SN, Mahmood AA, Chua KH, Vikineswary S, Kuppusamy UR

Evid Based Complement Alternat Med, 2013;2013:185259.
PMID: 23737819 DOI: 10.1155/2013/185259

Mushrooms have been used in folk medicine for thousands of years. In this study, the effect of β -glucan-rich extract of P. sajor-caju (GE) on lipid lowering and antioxidant potential was assessed in C57BL/6J mice fed on a high-fat diet. Obesity was induced in C57BL/6J mice by feeding a high-fat diet. The control groups in this study were ND (for normal diet) and HFD (for high-fat diet). The treated groups were ND240 (for normal diet) (240 mg/kg b.w) and HFD60, HFD120, and HFD240 (for high-fat diet), where the mice were administrated with three dosages of GE (60, 120, and 240 mg GE/kg b.w). Metformin (2 mg/kg b.w) served as positive control. GE-treated groups showed significantly reduced body weight, serum lipid, and liver enzymes levels. GE also attenuated protein carbonyl and lipid hydroperoxide levels by increasing the enzymic antioxidants (SOD, CAT, and GPx) activities in the mice. GE-treated groups induced the expression of hormone sensitive lipase (HSL) and adipose triglyceride lipase (ATGL) while downregulated the expression of peroxisome proliferator-activated receptor gamma (PPAR- γ ), sterol regulatory binding protein-1c (SREBP-1c), and lipoprotein lipase (LPL). Hence, GE prevented weight gain in the mice by inducing lipolysis and may be valuable in the formulation of adjuvant therapy for obesity.
Fulltext Betulinic Acid inhibits growth of cultured vascular smooth muscle cells in vitro by inducing g(1) arrest and apoptosis

Vadivelu RK, Yeap SK, Ali AM, Hamid M, Alitheen NB

Evid Based Complement Alternat Med, 2012;2012:251362.
PMID: 23056140 DOI: 10.1155/2012/251362

Betulinic acid is a widely available plant-derived triterpene which is reported to possess selective cytotoxic activity against cancer cells of neuroectodermal origin and leukemia. However, the potential of betulinic acid as an antiproliferative and cytotoxic agent on vascular smooth muscle (VSMC) is still unclear. This study was carried out to demonstrate the antiproliferative and cytotoxic effect of betulinic acid on VSMCs using 3-[4,5-dimethylthizol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometry cell cycle assay, BrdU proliferation assay, acridine orange/propidium iodide staining, and comet assay. Result from MTT and BrdU assays indicated that betulinic acid was able to inhibit the growth and proliferation of VSMCs in a dose-dependent manner with IC(50) of 3.8 μg/mL significantly (P < 0.05). Nevertheless, betulinic acid exhibited G(1) cell cycle arrest in flow cytometry cell cycle profiling and low level of DNA damage against VSMC in acridine orange/propidium iodide and comet assay after 24 h of treatment. In conclusion, betulinic acid induced G(1) cell cycle arrest and dose-dependent DNA damage on VSMC.
Fulltext Bioactive Markers Based Pharmacokinetic Evaluation of Extracts of a Traditional Medicinal Plant, Piper sarmentosum

Hussain K, Ismail Z, Sadikun A, Ibrahim P

Evid Based Complement Alternat Med, 2011;2011:980760.
PMID: 19770264 DOI: 10.1093/ecam/nep143

In vitro assays are economical and easy to perform but to establish relevance of their results to real clinical outcome in animals or human, pharmacokinetics is prerequisite. Despite various in vitro pharmacological activities of extracts of Piper sarmentosum, there is no report of pharmacokinetics. Therefore, the present study aimed to evaluate ethanol extract of fruit of the plant in dose of 500 mg kg(-1) orally for pharmacokinetics. Sprague-Dawley rats were randomly divided into groups 1, 2, and 3 (each n = 6) to study absorption, distribution and excretion, respectively. High performance liquid chromatography (HPLC) with ultraviolet detection was applied to quantify pellitorine, sarmentine and sarmentosine in plasma, tissues, feces and urine to calculate pharmacokinetic parameters. Pellitorine exhibited maximum plasma concentration (C(max)) 34.77 ng mL(-1) ± 1.040, time to achieve C(max) (T(max)) 8 h, mean resident time (MRT) 26.00 ± 0.149 h and half life (t(1/2)) 18.64 ± 1.65 h. Sarmentine showed C(max) 191.50 ± 12.69 ng mL(-1), T(max) 6 h, MRT 11.12 ± 0.44 h and t(1/2) 10.30 ± 1.98 h. Sarmentosine exhibited zero oral bioavailability because it was neither detected in plasma nor in tissues, and in urine. Pellitorine was found to be distributed in intestinal wall, liver, lungs, kidney, and heart, whereas sarmentine was found only in intestinal wall and heart. The cumulative excretion of pellitorine, sarmentine and sarmentosine in feces in 72 h was 0.0773, 0.976, and 0.438 μg, respectively. This study shows that pellitorine and sarmentine have good oral bioavailability while sarmentosine is not absorbed from the gastrointestinal tract.
Fulltext Bioassay-Guided Isolation of Cytotoxic Cycloartane Triterpenoid Glycosides from the Traditionally Used Medicinal Plant Leea indica

Wong YH, Abdul Kadir H, Ling SK

Evid Based Complement Alternat Med, 2012;2012:164689.
PMID: 22203865 DOI: 10.1155/2012/164689

Leea indica is a medicinal plant used traditionally to cure cancer. In this study, the cytotoxic compounds of L. indica were isolated using bioassay-guided approach. Two cycloartane triterpenoid glycosides, mollic acid arabinoside (MAA) and mollic acid xyloside (MAX), were firstly isolated from L. indica. They inhibited the growth of Ca Ski cervical cancer cells with IC(50) of 19.21 μM (MAA) and 33.33 μM (MAX). MRC5 normal cell line was used to calculate selectivity index. MAA and MAX were about 8 and 4 times more cytotoxic to Ca Ski cells compared to MRC5. The cytotoxicity of MAA was characterized by both cytostatic and cytocidal effects. MAA decreased the expression of proliferative cell nuclear antigen, increased sub-G1 cells, and arrested cells in S and G2/M phases. This study provides the evidence for the ethnomedicinal use of L. indica and paves the way for future mechanism studies on the anticancer effects of MAA.
Fulltext Boesenbergia rotunda: From Ethnomedicine to Drug Discovery

Eng-Chong T, Yean-Kee L, Chin-Fei C, Choon-Han H, Sher-Ming W, Li-Ping CT, et al.

Evid Based Complement Alternat Med, 2012;2012:473637.
PMID: 23243448 DOI: 10.1155/2012/473637

Boesenbergia rotunda is a herb from the Boesenbergia genera under the Zingiberaceae family. B. rotunda is widely found in Asian countries where it is commonly used as a food ingredient and in ethnomedicinal preparations. The popularity of its ethnomedicinal usage has drawn the attention of scientists worldwide to further investigate its medicinal properties. Advancement in drug design and discovery research has led to the development of synthetic drugs from B. rotunda metabolites via bioinformatics and medicinal chemistry studies. Furthermore, with the advent of genomics, transcriptomics, proteomics, and metabolomics, new insights on the biosynthetic pathways of B. rotunda metabolites can be elucidated, enabling researchers to predict the potential bioactive compounds responsible for the medicinal properties of the plant. The vast biological activities exhibited by the compounds obtained from B. rotunda warrant further investigation through studies such as drug discovery, polypharmacology, and drug delivery using nanotechnology.
Fulltext Bone Micro-CT Assessments in an Orchidectomised Rat Model Supplemented with Eurycoma longifolia

Ramli R, Khamis MF, Shuid AN

Evid Based Complement Alternat Med, 2012;2012:501858.
PMID: 22952556 DOI: 10.1155/2012/501858

Recent studies suggested that Eurycoma longifolia, a herbal plant, may have the potential to treat osteoporosis in elderly male. This study aimed to determine the effects of Eurycoma longifolia supplementation on the trabecular bone microarchitecture of orchidectomised rats (androgen-deficient osteoporosis model). Forty-eight-aged (10-12 months old) Sprague Dawley rats were divided into six groups of sham-operated (SHAM), orchidectomised control (ORX), orchidectomised + 7 mg/rat testosterone enanthate (TEN) and orchidectomised + Eurycoma longifolia 30 mg/kg (EL30), orchidectomised + Eurycoma longifolia 60 mg/kg (EL60), orchidectomised + Eurycoma longifolia 90 mg/kg (EL90). Rats were euthanized following six weeks of treatment. The left femora were used to measure the trabecular bone microarchitecture using micro-CT. Orchidectomy significantly decreased connectivity density, trabecular bone volume, and trabecular number compared to the SHAM group. Testosterone replacement reversed all the orchidectomy-induced changes in the micro-CT parameters. EL at 30 and 60 mg/kg rat worsened the trabecular bone connectivity density and trabecular separation parameters of orchidectomised rats. EL at 90 mg/kg rat preserved the bone volume. High dose of EL (90 mg/kg) may have potential in preserving the bone microarchitecture of orchidectomised rats, but lower doses may further worsen the osteoporotic changes.
Fulltext Brain Cortical and Hippocampal Dopamine: A New Mechanistic Approach for Eurycoma longifolia Well-Known Aphrodisiac Activity and Its Chemical Characterization

Ezzat SM, Ezzat MI, Okba MM, Hassan SM, Alkorashy AI, Karar MM, et al.

Evid Based Complement Alternat Med, 2019;2019:7543460.
PMID: 31275418 DOI: 10.1155/2019/7543460

Eurycoma longifolia Jack (Fam.: Simaroubaceae), known as Tongkat Ali (TA), has been known as a symbol of virility and sexual power for men. Metabolic profiling of the aqueous extract of E. longifolia (AEEL) using UPLC-MS/MS in both positive and negative modes allowed the identification of seventeen metabolites. The identified compounds were classified into four groups: quassinoids, alkaloids, triterpenes, and biphenylneolignans. AEEL is considered safe with oral LD50 cut-off >5000 mg/kg. Oral administration of 50, 100, 200, 400, or 800 mg/kg of AEEL for 10 consecutive days to Sprague-Dawley male rats caused significant reductions in mounting, intromission, and ejaculation latencies and increased penile erection index. AEEL increased total body weight and relative weights of seminal vesicles and prostate. Total and free serum testosterone and brain cortical and hippocampal dopamine content was significantly elevated in treated groups with no significant effects on serotonin or noradrenaline content.

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