Medicinal Potential of Isoflavonoids: Polyphenols That May Cure Diabetes.

In recent years, there is emerging evidence that isoflavonoids, either dietary or obtained from traditional medicinal plants, could play an important role as a supplementary drug in the management of type 2 diabetes mellitus (T2DM) due to their reported pronounced biological effects in relation to multiple metabolic factors associated with diabetes. Hence, in this regard, we have comprehensively reviewed the potential biological effects of isoflavonoids, particularly biochanin A, genistein, daidzein, glycitein, and formononetin on metabolic disorders and long-term complications induced by T2DM in order to understand whether they can be future candidates as a safe antidiabetic agent. Based on in-depth in vitro and in vivo studies evaluations, isoflavonoids have been found to activate gene expression through the stimulation of peroxisome proliferator-activated receptors (PPARs) (α, γ), modulate carbohydrate metabolism, regulate hyperglycemia, induce dyslipidemia, lessen insulin resistance, and modify adipocyte differentiation and tissue metabolism. Moreover, these natural compounds have also been found to attenuate oxidative stress through the oxidative signaling process and inflammatory mechanism. Hence, isoflavonoids have been envisioned to be able to prevent and slow down the progression of long-term diabetes complications including cardiovascular disease, nephropathy, neuropathy, and retinopathy. Further thoroughgoing investigations in human clinical studies are strongly recommended to obtain the optimum and specific dose and regimen required for supplementation with isoflavonoids and derivatives in diabetic patients.

Modulation of metabolic alterations of obese diabetic rats upon treatment with Salacca zalacca fruits extract using 1H NMR-based metabolomics.

Fruit of salak (Salacca zalacca) is traditionally used and commercialized as an antidiabetic agent. However, the scientific evidence to prove this traditional use is lacking. This research was aimed to evaluate the metabolic changes of obese-diabetic (OBDC) rats treated with S. zalacca fruit extract using proton-nuclear magnetic resonance (1H NMR)-based metabolomics approach. This research presents the first report on the in vitro antidiabetic effect of S. zalacca fruits extract using this approach. The obtained results indicated that the administration of 400 mg/kg bw of 60% ethanolic S. zalacca extract for 6 weeks significantly decreased the blood glucose level and normalized the blood lipid profile of the OBDC rats. The potential biomarkers in urine were 2-oxoglutarate, alanine, leucine, succinate 3-hydroxybutyrate, taurine, betaine, allantoin, acetate, dimethylamine, creatine, creatinine, glucose, phenyl-acetylglycine, and hippurate. Based on the data obtained, the 60% ethanolic extract could not fully improved the metabolic complications of diabetic rats. The extract of S. zalacca fruit was able to decrease the ketones bodies as 3-hydroxybutyrate and acetoacetate. It also improved energy metabolism, involving glucose, acetate, lactate, 2-hydroxybutyrate, 2-oxoglutarate, citrate, and succinate. Moreover, it decreased metabolites from gut microflora, including choline. This extract had significant effect on amino acid metabolism, metabolites from gut microflora, bile acid metabolism and creatine. The result can further support the traditional claims of S. zalacca fruits in management of diabetes. This finding might be valuable in understanding the molecular mechanism and pharmacological properties of this medicinal plant for managing diabetes mellitus.

Investigation of α-Glucosidase Inhibitory Metabolites from Tetracera scandens Leaves by GC-MS Metabolite Profiling and Docking Studies.

Stone leaf (Tetracera scandens) is a Southeast Asian medicinal plant that has been traditionally used for the management of diabetes mellitus. The underlying mechanisms of the antidiabetic activity have not been fully explored yet. Hence, this study aimed to evaluate the α-glucosidase inhibitory potential of the hydromethanolic extracts of T. scandens leaves and to characterize the metabolites responsible for such activity through gas chromatography-mass spectrometry (GC-MS) metabolomics. Crude hydromethanolic extracts of different strengths were prepared and in vitro assayed for α-glucosidase inhibition. GC-MS analysis was further carried out and the mass spectral data were correlated to the corresponding α-glucosidase inhibitory IC50 values via an orthogonal partial least squares (OPLS) model. The 100%, 80%, 60% and 40% methanol extracts displayed potent α-glucosidase inhibitory potentials. Moreover, the established model identified 16 metabolites to be responsible for the α-glucosidase inhibitory activity of T. scandens. The putative α-glucosidase inhibitory metabolites showed moderate to high affinities (binding energies of -5.9 to -9.8 kcal/mol) upon docking into the active site of Saccharomyces cerevisiae isomaltase. To sum up, an OPLS model was developed as a rapid method to characterize the α-glucosidase inhibitory metabolites existing in the hydromethanolic extracts of T. scandens leaves based on GC-MS metabolite profiling.

GC-MS analysis of metabolites from soxhlet extraction, ultrasound-assisted extraction and supercritical fluid extraction of Salacca zalacca flesh and its alpha-glucosidase inhibitory activity.

Different extraction processes were employed to extract bioactive metabolites from Salacca zalacca flesh by a range of aqueous and organic solvents. The highest extraction yield was obtained by 50% ethanol extract of SE (73.18 ± 4.35%), whereas SFE_1 showed the lowest yield (0.42 ± 0.08%). All extracts were evaluated for in vitro α-glucosidase inhibitory activity, measured by their IC50 values in comparison to that of quercetin, the positive control (IC50 = 2.7 ± 0.7 µg/mL). The lowest α-glucosidase inhibitory activity was indicated by water extract of SE (IC50 = 724.3 ± 42.9 µg/mL) and the highest activity was demonstrated by 60% ethanol extract by UAE (IC50 = 16.2 ± 2.4 µg/mL). All extracts were analysed by GC-MS and identified metabolites like carbohydrates, fatty acids, organic acids, phenolic acids, sterols and alkane-based compounds etcetera that may possess the potential as α-glucosidase inhibitor and may attribute to the α-glucosidase inhibitory activity.

Correlation of FT-IR Fingerprint and α-Glucosidase Inhibitory Activity of Salak (Salacca zalacca) Fruit Extracts Utilizing Orthogonal Partial Least Square.

Salak fruit (Salacca zalacca), commonly known as snake fruit, is used indigenously as food and for medicinal applications in Southeast Asia. This study was conducted to evaluate the α-glucosidase inhibitory activity of salak fruit extracts in correlation to its Fourier transform infrared spectroscopy (FT-IR) fingerprint, utilizing orthogonal partial least square. This calibration model was applied to develop a rapid analytical method tool for quality control of this fruit. A total of 36 extracts prepared with different solvent ratios of ethanol⁻water (100, 80, 60, 40.20, 0% v/v) and their α-glucosidase inhibitory activities determined. The FT-IR spectra of ethanol⁻water extracts measured in the region of 400 and 4000 cm−1 at a resolution of 4 cm−1. Multivariate analysis with a combination of orthogonal partial least-squares (OPLS) algorithm was used to correlate the bioactivity of the samples with the FT-IR spectral data. The OPLS biplot model identified several functional groups (C⁻H, C=O, C⁻N, N⁻H, C⁻O, and C=C) which actively induced α-glucosidase inhibitory activity.

α-Glucosidase Inhibitory Activity of Selected Malaysian Plants.

Diabetes is a common metabolic disease indicated by unusually high plasma glucose level that can lead to major complications such as diabetic neuropathy, retinopathy, and cardiovascular diseases. One of the effective therapeutic managements of the disease is to reduce postprandial hyperglycemia through inhibition of α-glucosidase, a carbohydrate-hydrolyzing enzyme to retard overall glucose absorption. In recent years, a plenty of research works have been conducted looking for novel and effective α-glucosidase inhibitors (AGIs) from natural sources as alternatives for the synthetic AGI due to their unpleasant side effects. Plants and herbs are rich with secondary metabolites that have massive pharmaceutical potential. Besides, studies showed that phytochemicals such as flavonoids, alkaloids, terpenoids, anthocyanins, glycosides, and phenolic compounds possess significant inhibitory activity against α-glucosidase enzyme. Malaysia is a tropical country that is rich with medicinal herbs. In this review, we focus on eight Malaysian plants with the potential as AGI to develop a potential functional food or lead compounds against diabetes.

Moxibustion (Artemisia Plant at Acupuncture Point) as Alternative Therapy in Hypertension: A Promising Approach.

Hypertension is a pathological condition in which the blood pressure is higher than under normal physiological conditions, i.e., 140/90 mmHg or higher. Blood pressure is measured as the force exerted by the blood pumped by the heart against the walls of arteries (aorta) and distributed throughout the body. Use of complementary and alternative medicine as a cure for hypertension is a common phenomenon because of the high risk of cardiovascular complications and kidney diseases caused by conventional Western medicine. It is reported that high blood pressure causes ~49% of myocardial infarction and 62% of strokes. Effective treatment of hypertension is restricted by adverse effects and cost of the medication. Moxibustion is the application of heat by burning a small bundle of tightly bound moxa, to targeted acupoint, and sometimes it is used along with acupuncture. Encouraging results have been reported on randomized trials indicating the efficacy of moxibustion. But more controlled clinical trials are required to further establish the potential efficacy of moxibustion approach in hypertension.

Use of Complementary and Alternative Medicine among Osteoarthritic Patients: A Review.

INTRODUCTION: One of the most important indications of complementary and alternative medicines (CAM) is in arthritis. The popularity of CAM in arthritis is consistently on the rise because of the potential side effects of the conventional therapy (Methotrexate) of arthritis. In view of this, it was important to summarize the information, for healthcare professionals and the patients, about the safety and effectiveness of various CAM use in arthritis. MATERIALS AND METHODS: This comprehensive review is based on the content derived through a thorough literature search using 5 electronic databases such as Science direct, Springer link, PubMed, Jet P and Google scholar. Equivalent terms in thesauruses or Medical Subject Heading (MeSH) browsers were used whenever possible. We included all the articles those are used CAM medications for the treatment of arthritis around the globe and searched for the required articles published in English in peer reviewed journals from January 1999 to February 2014. Reports were then arranged and analysed on the basis of country specific studies. RESULTS: Initially, a total of 156 articles were retrieved, after further screening, 27 articles were selected according to meet objectives of the study and those articles which did not qualify, were excluded. Seventeen appropriate studies were finally included in the review. Indeed most of the studies that fulfilled the objective of this review were carried out in US (n=8, 47%), then in India (n=2, 11.76%), UK (n=1, 5.88%), Canada (n=1, 5.88%), Australia (n=1, 5.88%), Korea (n=1, 5.88%), Thailand (n=1, 5.88%), Turkey (n=1, 5.88%) and Malaysia (n=1, 5.88%). CONCLUSION: The review revealed that family, friend, past experiences and lack of effectiveness of conventional therapy are the major factors that influenced patients' decision of initiating and persisting with CAM therapy. The review highlighted the need to conduct future studies by using some more specific health related outcome measures.

Role of complementary and alternative medicine in geriatric care: A mini review.

Since time immemorial homo sapiens are subjected to both health and diseases states and seek treatment for succor and assuagement in compromised health states. Since last two decades the progressive rise in the alternative form of treatment cannot be ignored and population seems to be dissatisfied with the conventional treatment modalities and therefore, resort to other forms of treatment, mainly complementary and alternative medicine (CAM). The use of CAM is predominantly more popular in older adults and therefore, numerous research studies and clinical trials have been carried out to investigate the effectiveness of CAM in the management of both communicable and non-communicable disease. In this current mini review, we attempt to encompass the use of CAM in chronic non-communicable diseases that are most likely seen in geriatrics. The current review focuses not only on the reassurance of good health practices, emphasizing on the holistic development and strengthening the body's defense mechanisms, but also attempts to construct a pattern of self-care and patient empowerment in geriatrics. The issues of safety with CAM use cannot be sidelined and consultation with a health care professional is always advocated to the patient. Likewise, responsibility of the health care professional is to inform the patient about the safety and efficacy issues. In order to substantiate the efficacy and safety of CAMs, evidence-based studies and practices with consolidated standards should be planned and executed.

Reasons of using complementary and alternative medicines (CAM) among elderly Malaysians of Kuala Lumpur and Selangor states: An exploratory study.

BACKGROUND: This study is aimed to explore the types of CAM and reasons of using CAM among elderly Malaysians. METHOD: This cross-sectional study was conducted on a sample of 256 conveniently selected elderly Malaysians who were residing in the states of Selangor and Kuala Lumpur. A pre-validated interview-administered questionnaire was used to gather information. Data was entered into PASW version 18 and analyzed. RESULTS: A total of 256 questionnaires were included in the study. A response rate of 64% was achieved. Out of 256 respondents, 92 (35.9%) were male while 164 (64.1%) were female. More than half of the respondents (n = 141; 55.1%) agreed that CAM is more effective than allopathic medicine. Chinese respondents showed strong belief in the effectiveness of CAM. In terms of safety of CAM, close to three quarters of respondents (n = 178; 69.5%) believed that CAM is safer than allopathic medicine. A large majority of respondents agreed that CAM has less side effects compared to allopathic medicine (n = 201; 78.5%) and also agreed that CAM is good to maintain overall health and wellbeing (n = 212; 82.8%). A majority of the respondents expressed that they use CAM because allopathic medicine is less effective (n = 113; 44.1%). CONCLUSION: The current study reflects the reasons of using CAM among lay public from different ethnicities. There are no reports of adverse effects related to CAM use. Future approaches should be intended for awareness campaigns for consumers, highlighting safety profile of CAM and as well as forbidding their use without the consultation of healthcare professional.

Potent α-glucosidase and α-amylase inhibitory activities of standardized 50% ethanolic extracts and sinensetin from Orthosiphon stamineus Benth as anti-diabetic mechanism.

BACKGROUND: In the present study, we tested a 50% ethanolic extract of Orthosiphon stamineus plants and its isolated bioactive compound with respect to their α-glucosidase and α-amylase inhibitory activities. METHODS: Bioactive flavonoid sinensetin was isolated from 50% ethanolic extract of Orthosiphon stamineus. The structure of this pure compound was determined on the NMR data and the α-glucosidase and α-amylase inhibitory activities of isolated sinensetin and 50% ethanolic extract of Orthosiphon stamineus were evaluated. RESULTS: In vitro studies of a 50% ethanolic extract of O. stamineus and the isolated sinensetin compound showed inhibitory activity on α-glucosidase (IC50: 4.63 and 0.66 mg/ml, respectively) and α-amylase (IC50: 36.70 mg/ml and 1.13 mg/ml, respectively). Inhibition of these enzymes provides a strong biochemical basis for the management of type 2 diabetes via the control of glucose absorption. CONCLUSION: Alpha-glucosidase and α-amylase inhibition could the mechanisms through which the 50% ethanolic extract of O. stamineus and sinensetin exert their antidiabetic activity, indicating that it could have potential use in the management of non-insulin-dependent diabetes.

Simultaneous determination of secondary metabolites from Vinca rosea plant extractives by reverse phase high performance liquid chromatography.

BACKGROUND: Vinca rosea (Apocynaceae) is one of the most important and high value medicinal plants known for its anticancer alkaloids. It is the iota of the isolated secondary metabolites used in chemotherapy to treat diverse cancers. Several high performance liquid chromatography (HPLC) methods have been developed to quantify the active alkaloids in the plant. However, this method may serve the purpose in quantification of V. rosea plant extracts in totality. OBJECTIVE: To develop and validate the reverse phase (RP)-HPLC method for simultaneous determination of secondary metabolites, namely alkaloids from V. rosea plant extracts. MATERIALS AND METHODS: The quantitative determination was conducted by RP-HPLC equipped with ultraviolet detector. Optimal separation was achieved by isocratic elution with mobile phase consisting of methanol:acetonitrile:ammonium acetate buffer (25 mM) with 0.1% triethylamine (15:45:40 v/v) on a column (Zorbax Eclipse plus C(18), 250 mm % 4.6 mm; 5 µm). The standard markers (vindoline, vincristine, catharanthine, and vinblastine) were identified by retention time and co-injected with reference standard and quantified by external standard method at 297 nm. RESULTS: The precision of the method was confirmed by the relative standard deviation (R.S.D.), which was lower than 2.68%. The recoveries were in the range of 98.09%-108%. The limits of detection (LOD) for each marker alkaloids were lower than 0.20 µg. Different parts of the V. rosea extracts shows different concentrations of markers, flower samples were high in vinblastine content, while methanol extract from the leaves contains all the four alkaloids in good yield, and there is no significant presence of markers in water extracts. CONCLUSION: HPLC method established is appropriate for the standardization and quality assurance of V. rosea plant extracts.

Pharmacological mechanisms underlying the vascular activities of Loranthus ferrugineus Roxb. in rat thoracic aorta.

AIM OF THE STUDY: The present study was aimed to investigate the pharmacological basis for the use of Loranthus ferrugineus in hypertension. MATERIALS AND METHODS: Loranthus ferrugineus methanol extract (LFME) was obtained using Soxhelt extractor and then successively fractionated using chloroform, ethyl acetate and n-butanol. The n-butanol fraction of LFME (NBF-LFME) was studied using isolated rat thoracic aorta. RESULTS: NBF-LFME (1.0 x 10(-5) to 3.0mg/ml) was found to be the most potent to concentration-dependently relax the endothelium-intact phenyephrine (PE, 1 microM)- and high K(+) (80 mM)-precontracted rat aortic rings. Removal of the endothelium completely abolished the vascular relaxing properties of NBF-LFME. Pretreatment with atropine (1 microM), L-NAME (10 microM), indomethacin (10 microM) and methylene blue (10 microM) significantly blocked NBF-LFME-mediated relaxation. Endothelium-dependent and -independent relaxations induced by acetylcholine (ACh) and sodium nitroprusside (SNP), respectively, were significantly enhanced in aortic rings pretreated with NBF-LFME when compared to those observed in control aortic rings. On the contrary, glibenclamide (10 microM), propranolol (1 microM) and prazosin (0.01 microM) did not alter NBF-LFME-induced relaxation. CONCLUSIONS: The results suggest that NBF-LFME induced vascular relaxation by stimulating muscarinic receptors, activating the endothelium-derived nitric oxide-cGMP-relaxant pathway, promoting prostacyclin release and/or possibly through its ability to lengthen the released nitric oxide half-life. The present data further supports previous in vivo findings and explain the traditional use of Loranthus ferrugineus as an anti-hypertensive agent.

Characterization of the possible mechanisms underlying the hypotensive and spasmogenic effects of Loranthus ferrugineus methanolic extract.

In the present study, L. ferrugineus methanol extract (LFME) was evaluated for its blood pressure lowering effect in anesthetized normotensive Sprague Dawley (SD) rats and its spasmogenic effect in isolated guinea pig ileum. The possible mechanism(s) of action were also investigated. LFME was obtained by Soxhlet extraction. The rats were fasted overnight and anesthetized with sodium pentobarbitone (60 mg/kg i.p.). LFME was administered in i.v. boluses in the concentrations of 25, 50, 100 and 200 mg/kg respectively, with concomitant monitoring of mean arterial pressure (MAP). It was found that LFME dose-dependently reduced MAP. An i.v. bolus injection of atropine significantly decreased the blood pressure lowering effect of LFME. Similarly, L-NAME (Nomega-nitro-L-arginine methyl ester) significantly lowered both the MAP and the action duration. Conversely, no significant change in MAP was seen following i.v. injections of neostigmine, hexamethonium, prazosin and propranolol. LFME also produced a dose-dependent contractile effect in guinea pig ileum. This contraction was significantly reduced in atropine pre-incubated tissue segments, yet it was significantly enhanced in the presence of neostigmine. No appreciable change in the ability of LFME to contract guinea pig ileum was seen in the presence of hexamethonium. Accordingly, it can be postulated that LFME possesses a marked hypotensive effect that can be attributed to stimulation of muscarinic receptors and/or stimulation of nitric oxide (NO) release. Moreover, LFME retains a considerable spasmogenic action due to its cholinergic properties. The hypotensive and spasmogenic effects of LFME justify its traditional uses.

In vitro cholinomimetic effect of Loranthus ferrugineus in isolated guinea pig ileum.

This study aimed to elucidate the mechanism(s) of the spasmogenic action of Loranthus ferrugineus in isolated guinea pig ileum. Thus the contractile responses of guinea pig ileum to graded additions of either L. ferrugineus methanol extract or its n-butanol fraction were tested in the presence and absence of various pharmacological interventions. The data showed that L. ferrugineus methanol extract and the n-butanol fraction produced a concentration-dependent spasmogenic effect in isolated guinea pig ileum segments. These effects were significantly inhibited in the presence of 1 microM atropine. In contrast, the response to the lowest concentrations of L. ferrugineus methanol extract (0.25, 0.5 and 1 mg/mL) and n-butanol fraction of L. ferrugineus (0.125, 0.25 and 0.5 mg/mL) were considerably enhanced in the presence of 0.05 microM neostigmine. Neither L. ferrugineus methanol extract nor n-butanol fraction contractile responses were affected upon the incubation of the ileal segments with 100 microM hexamethonium. The results of this study show that the spasmogenic effect of L. ferrugineus is possibly mediated through a direct action on intestinal muscarinic receptors. It is suggested that the bioactive constituents of L. ferrugineus serve as a substrate for acetylcholinesterase.