AIM OF THE STUDY: To investigate the wound healing ability of a concentrated extract of B. orientale in a hydrogel formulation in healing diabetic ulcer wounds.
MATERIALS AND METHODS: The water extract from the leaves of B. orientale was separated from the crude methanolic extract and subjected to flash column chromatography techniques to produce concentrated fractions. These fractions were tested for phytochemical composition, tannin content, antioxidative and antibacterial activity. The bioactive fraction was formulated into a sodium carboxymethylcellulose hydrogel. The extract-loaded hydrogels were then characterized and tested on excision ulcer wounds of streptozotocin-induced diabetic rats. Wound size was measured for 14 days. Histopathological studies were conducted on the healed wound tissues to observe for epithelisation, fibroblast proliferation and angiogenesis. All possible mean values were subjected to statistical analysis using One-way ANOVA and post-hoc with Tukey's T-test (P<0.05).
RESULTS: One fraction exhibited strong antioxidative and antibacterial activity. The fraction was also highly saturated with tannins, particularly condensed tannins. Fraction W5-1 exhibited stronger antioxidant activity compared to three standards (α-Tocopherol, BHT and Trolox-C). Antibacterial activity was also present, and notably bactericidal towards Methicillin-resistant Staphylococcus aureus (MRSA) at 0.25mg/ml. The extract-loaded hydrogels exhibited shear-thinning properties, with high moisture retention ability. The bioactive fraction at 4% w/w was shown to be able to close diabetic wounds by Day 12 on average. Other groups, including controls, only exhibited wound closure by Day 14 (or not at all). Histopathological studies had also shown that extract-treated wounds exhibited re-epithelisation, higher fibroblast proliferation, collagen synthesis, and angiogenesis.
CONCLUSION: The ethnopharmacological effects of using B. orientale as a topical treatment for external wounds was validated and was also significantly effective in treating diabetic ulcer wounds. Thus, B. orientale extract hydrogel may be presented as a potential treatment for diabetic ulcer wounds.
AIMS OF THE STUDY: This study aims to investigate the ability of T. diffusa to ameliorate the impairment in testicular steroidogenesis and spermatogenesis in DM that might help to improve testicular function, and subsequently restore male fertility.
MATERIALS AND METHODS: DM-induced adult male rats were given 100 mg/kg/day and 200 mg/kg/day T. diffusa leaf extract orally for 28 consecutive days. Rats were then sacrificed; sperm and testes were harvested and sperm parameter analysis were performed. Histo-morphological changes in the testes were observed. Biochemical assays were performed to measure testosterone and testicular oxidative stress levels. Immunohistochemistry and double immunofluorescence were used to monitor oxidative stress and inflammation levels in testes as well as Sertoli and steroidogenic marker proteins' expression.
RESULTS: Treatment with T. diffusa restores sperm count, motility, and viability near normal and reduces sperm morphological abnormalities and sperm DNA fragmentation in diabetic rats. T. diffusa treatment also reduces testicular NOX-2 and lipid peroxidation levels, increases testicular antioxidant enzymes (SOD, CAT, and GPx) activities, ameliorates testicular inflammation via downregulating NF-ΚB, p-Ikkβ and TNF-α and upregulating IκBα expression. In diabetic rats, T. diffusa treatment increases testicular steroidogenic proteins (StAR, CYP11A1, SHBG, and ARA54, 3 and 17β-HSD) and plasma testosterone levels. Furthermore, in diabetic rats treated with T. diffusa, Sertoli cell marker proteins including Connexin 43, N-cadherin, and occludin levels in the testes were elevated.
CONCLUSION: T. diffusa treatment could help to ameliorate the detrimental effects of DM on the testes, thus this plant has potential to be used to restore male fertility.
AIM OF THE REVIEW: This paper aimed to provide a critical review of current scenario on K. galanga. This review provides a current data on diversity, phytochemistry, pharmacological activities and traditional uses of K. galanga.
MATERIALS AND METHODS: The information and data on K. galanga were collated from various resources like ethnobotanical textbooks and literature databases such as PubMed, Science Direct, Wiley, Springer, Tailor and Francis, Scopus, Inflibnet, Google and Google Scholar.
RESULTS: The forty-nine phytochemicals including esters, terpenoids, flavonoids, thiourea derivatives, polysaccharides, diarylheptanoids, phenolic acids, phenolic glycoside and cyclic lipodepsipeptide have been hitherto isolated and characterized. The major bioactive compounds extracted from the rhizome of K. galanga were ethyl p-methoxycinnamate, ethyl cinnamate, kaempferol, kaempferide, kaempsulfonic acids, kaemgalangol A, xylose, cystargamide B and 3-caren-5-one. Various studies demonstrated that the K. galanga and its constituents possess several pharmacological activities like antimicrobial, antioxidant, amebicidal, analgesic, anti-inflammatory, anti-tuberculosis, anti-dengue, anti-nociceptive, anti-angiogenic, anticancer, hyperlipidemic, hypopigmentary, osteolysis, larvicidal, insecticidal and mosquito repellent, nematocidal, sedative, sniffing, vasorelaxant and wound healing.
CONCLUSION: Kaempferia galanga L. is a valuable medicinal plant which is used traditionally in India to treat a wide variety of ailments. A number of bioactive phytochemicals like esters, terpenoids, flavonoids, polysaccharides, diarylheptanoids, cyclic lipodepsipeptide, phenolic acids and glucoside have been isolated from the rhizomes of K. galanga by several researchers. These phytochemicals are highly bioactive and exhibit various pharmacological activities.
AIM OF THE STUDY: As allergy could be mediated by both IgE and IgG, we further evaluated the anti-allergy potential of CNAE in both in vitro model of IgG-induced macrophage activation and in vivo anaphylaxis models to further dissect the mechanism of action underlying the anti-allergic properties of CNAE.
MATERIAL & METHODS: The anti-allergy potential of CNAE was evaluated in in vivo anaphylaxis models of ovalbumin-challenged active systemic anaphylaxis (OVA-ASA) and IgE-challenged passive systemic anaphylaxis (PSA) using Sprague Dawley rats as well as IgG-challenged passive systemic anaphylaxis (IgG-PSA) using C57BL/6 mice. Meanwhile, in vitro model of IgG-induced macrophage activation model was performed using IC-21 macrophages. The release of soluble mediators from both IgE and IgG-mediated pathways were measured using enzyme-linked immunosorbent assay (ELISA). The signaling molecules targeted by CNAE were identified by performing Western blot.
RESULTS: IgG, platelet-activating factor (PAF) and IL-6 was suppressed by CNAE in OVA-ASA, but not IgE. In addition, CNAE significantly suppressed PAF and IL-6 in IgG-PSA but did not suppress histamine, IL-4 and leukotrienes C4 (LTC4) in IgE-PSA. CNAE also inhibited IL-6 and TNF-α by inhibiting the phosphorylation of ERK1/2 in the IgG-induced macrophage activation model.
CONCLUSION: Overall, our findings supported that CNAE exerts its anti-allergic properties by suppressing the IgG pathway and its mediators by inhibiting ERK1/2 phosphorylation, thus providing scientific evidence supporting its traditional use in managing allergy.
MATERIALS AND METHODS: International and Thai databases were searched from inception to February 2017. Clinical trials investigating effects of PM menopausal or postmenopausal women were included. Outcomes were self-reported menopausal symptoms, serum reproductive hormones, urino-genital tract function, and bone surrogates. Methodological quality was assessed by Cochrane risk-of-bias v2.0, and a 22-parameter quality score based on the CONSORT checklist for herbal medicines.
RESULTS: Eight studies (9 articles) used data from 309 menopausal patients. Five-studies demonstrated that PM was associated with climacteric scores reduced by ~50% compared to baseline. Other PM studies using limited numbers of placebo participants suggested improved vaginal and other urogenital tract symptoms. Bone alkaline phosphatase halved (suggesting lowered bone turnover). Variable serum reproductive hormone levels suggested menopausal status differed between studies. PM active ingredients and sources were not defined. Adverse event rates (mastodynia, vaginal spotting, dizziness) were similar in all groups (PM, conjugated equine estrogen, and placebos) but serum C-reactive protein doubled. These studies had design and reporting deficiencies, high risks of biases, and low quality scores.
CONCLUSIONS: The efficacy of PM on menopausal symptoms remains inconclusive because of methodological short-comings especially placebo effects inherent in self-assessment/recall questionnaires and no PM standardization. PM efficacy and safety need a fundamental re-appraisal by: (i) cohort (retro- and prospective) studies on current users to define its traditional use for rejuvenation; (ii) tightly coupling long-term efficacy to safety of well-defined PM and multiple end-points; (iii) using study design related to current understanding of menopause progression and estrogen pharmacology (iv) robust pharmacovigilance.
AIM OF THE STUDY: The molecular mechanisms of the anti-inflammatory properties of M. accedens are not yet understood. Therefore, we examined those mechanisms using a methanol extract of M. accedens (Ma-ME) and determined the target molecule in macrophages.
MATERIALS AND METHODS: We evaluated the anti-inflammatory effects of Ma-ME in lipopolysaccharide (LPS)-stimulated RAW264.7 cells and in an HCl/EtOH-triggered gastritis model in mice. To investigate the anti-inflammatory activity, we performed a nitric oxide (NO) production assay and ELISA assay for prostaglandin E2 (PGE2). RT-PCR, luciferase gene reporter assays, western blotting analyses, and a cellular thermal shift assay (CETSA) were conducted to identify the mechanism and target molecule of Ma-ME. The phytochemical composition of Ma-ME was analyzed by HPLC and LC-MS/MS.
RESULTS: Ma-ME suppressed the production of NO and PGE2 and the mRNA expression of proinflammatory genes (iNOS, IL-1β, and COX-2) in LPS-stimulated RAW264.7 cells without cytotoxicity. Ma-ME inhibited NF-κB activation by suppressing signaling molecules such as IκBα, Akt, Src, and Syk. Moreover, the CETSA assay revealed that Ma-ME binds to Syk, the most upstream molecule in the NF-κB signal pathway. Oral administration of Ma-ME not only alleviated inflammatory lesions, but also reduced the gene expression of IL-1β and p-Syk in mice with HCl/EtOH-induced gastritis. HPLC and LC-MS/MS analyses confirmed that Ma-ME contains various anti-inflammatory flavonoids, including quercetin, daidzein, and nevadensin.
CONCLUSIONS: Ma-ME exhibited anti-inflammatory activities in vitro and in vivo by targeting Syk in the NF-κB signaling pathway. Therefore, we propose that Ma-ME could be used to treat inflammatory diseases such as gastritis.
AIM OF THE REVIEW: This review aims to present up-to-date information regarding the taxonomy, botany, distribution, ethnomedicinal uses, phytochemistry, pharmacology and toxicological profile of G. pentaphylla. The presented information was analyzed critically to understand current work undertaken on this species and explore possible future prospects for this plant in pharmaceutical research.
MATERIALS & METHODS: Bibliographic databases, including Google Scholar, PubMed, Web of Science, ScienceDirect, SpringerLink, Wiley Online Library, Semantic Scholar, Europe PMC, Scopus, and MEDLINE, were explored thoroughly for the collection of relevant information. The structures of phytoconstituents were confirmed with PubChem and SciFinder databases. Taxonomical information on the plant was presented in accordance with The Plant List (version 1.1).
RESULTS: Extensive phytochemical investigations into different parts of G. pentaphylla have revealed the presence of at least 354 secondary metabolites belonging to structurally diverse classes including alkaloids, amides, phenolic compounds, flavonoids, glycosides, aromatic compounds, steroids, terpenoids, and fatty derivatives. A large number of in vitro and in vivo experiments have demonstrated that G. pentaphylla had anticancer, antimutagenic, antibacterial, antifungal, anthelmintic, mosquitocidal, antidiabetic, antihyperlipidemic, anti-oxidant, anti-inflammatory, analgesic, antipyretic, anti-arsenicosis, and wound healing properties. Toxicological studies have established the absence of any significant adverse reactions and showed that the plant had a moderate safety profile.
CONCLUSIONS: G. pentaphylla can be suggested as a source of inspiration for the development of novel drugs, especially anticancer, antimicrobial, anthelmintic, and mosquitocidal agents. Moreover, bioassay-guided investigations into its diverse classes of secondary metabolites, especially the large pool of nitrogen-containing alkaloids and amides, promises the development of novel drug candidates. Future pharmacological studies into this species are also warranted as many of its traditional uses are yet to be validated scientifically.
AIM: The present study was conducted to investigate the possible mechanism of actions underlying the systemic antinociception activity of the essential oil of Zingiber zerumbet (EOZZ) in chemical-induced nociception tests in mice.
MATERIALS AND METHODS: Acetic acid-induced abdominal constriction, capsaicin-, glutamate- and phorbol 12-myristate 13-acetate-induced paw licking tests in mice were employed in the study. In all experiments, EOZZ was administered systemically at the doses of 50, 100, 200 and 300 mg/kg.
RESULTS: It was shown that EOZZ given to mice via intraperitoneal and oral routes at 50, 100, 200 and 300 mg/kg produced significant dose dependent antinociception when assessed using acetic acid-induced abdominal writing test with calculated mean ID(50) values of 88.84 mg/kg (80.88-97.57 mg/kg) and 118.8 mg/kg (102.5-137.8 mg/kg), respectively. Likewise, intraperitoneal administration of EOZZ at similar doses produced significant dose dependent inhibition of neurogenic pain induced by intraplantar injection of capsaicin (1.6 μg/paw), glutamate (10 μmol/paw) and phorbol 12-myristate 13-acetate (1.6μg/paw) with calculated mean ID(50) of 128.8 mg/kg (118.6-139.9 mg/kg), 124.8 mg/kg (111.4-139.7 mg/kg) and 40.29 (35.39-45.86) mg/kg, respectively. It was also demonstrated that pretreatment with l-arginine (100mg/kg, i.p.), a nitric oxide precursor significantly reversed antinociception produced by EOZZ suggesting the involvement of l-arginine/nitric oxide pathway. In addition, methylene blue (20mg/kg, i.p.) significantly enhanced antinociception produced by EOZZ. Administration of glibenclamide (10mg/kg, i.p.), an ATP-sensitive K(+) channel antagonist significantly reversed antinociceptive activity induced by EOZZ.
CONCLUSION: Together, the present results suggested that EOZZ-induced antinociceptive activity was possibly related to its ability to inhibit glutamatergic system, TRPV1 receptors as well as through activation of l-arginine/nitric oxide/cGMP/protein kinase C/ATP-sensitive K(+) channel pathway.
AIM OF THE STUDY: The purpose of this study was to determine the in situ cytotoxicity effect P. macrocarpa fruit ethyl acetate fraction (PMEAF) and the underlying molecular mechanism of cell death.
MATERIALS AND METHODS: MDA-MB-231 cells were incubated with PMEAF for 24h. Cell cycle and viability were examined using flow cytometry analysis. Apoptosis was determined using the Annexin V assay and also by fluorescence microscopy. Apoptosis protein profiling was detected by RayBio® Human Apoptosis Array.
RESULTS: The AO/PI staining and flow cytometric analysis of MDA-MB-231 cells treated with PMEAF were showed apoptotic cell death. The cell cycle analysis by flow cytometry analysis revealed that the accumulation of PMEAF treated MDA-MB-231 cells in G0/G1 and G2/M-phase of the cell cycle. Moreover, the PMEAF exert cytotoxicity by increased the ROS production in MDA-MB-231 cells consistently stimulated the loss of mitochondrial membrane potential (∆Ψm) and induced apoptosis cell death by activation of numerous signalling proteins. The results from apoptosis protein profiling array evidenced that PMEAF stimulated the expression of 9 pro-apoptotic proteins (Bax, Bid, caspase 3, caspase 8, cytochrome c, p21, p27, p53 and SMAC) and suppressed the 4 anti-apoptotic proteins (Bcl-2, Bcl-w, XIAP and survivin) in MDA-MB-231 cells.
CONCLUSION: The results indicated that PMEAF treatment induced apoptosis in MDA-MB-231 cells through intrinsic mitochondrial related pathway with the participation of pro and anti-apoptotic proteins, caspases, G0/G1 and G2/M-phases cell cycle arrest by p53-mediated mechanism.
AIM OF THE STUDY: Recent studies have demonstrated a potent anticancer potential of P. macrocarpa, especially against HeLa cell. The objective of this study was to investigate the regulation of miRNAs on MDA-MB-231 treated with P. macrocarpa ethyl acetate fraction (PMEAF).
MATERIALS AND METHODS: The regulation of miRNAs on MDA-MB-231 cells treated with PMEAF was studied through IIlumina, Hi-Seq. 2000 platform of Next Generation Sequencing (NGS) and various in silico bioinformatics tools.
RESULTS: The PMEAF treatment against MDA-MB-231 cells identified 10 upregulated and 10 downregulated miRNAs. A set of 606 target genes of 10 upregulated miRNAs and 517 target genes of 10 downregulated miRNAs were predicted based on computational and validated databases by using miRGate DB Query. Meanwhile, results from DAVID Bioinformatics Resources 6.8 specified the functional annotation of the upregulated miRNAs involvement in cancer pathway by suppressing the oncogenes and downregulating miRNAs by expressing the tumour suppressor genes in the regulation of apoptosis pathway.
CONCLUSION: In conclusion, the results of this study proved that PMEAF is a promising anticancer agent with high cytotoxicity against MDA-MB-231 breast cancer cells and it induced apoptotic cell death mechanism through the regulation of miRNAs. PMEAF might be the best candidate for developing more potent anticancer drugs or chemo preventive supplements.
AIM OF THE STUDY: To provide pharmacological information on the active constituents evaluated in the preclinical study to treat epilepsy with potential to be used as an alternative therapeutic option in future. It also provides affirmation for the development of novel antiepileptic drugs derived from medicinal plants.
MATERIALS AND METHODS: Relevant information on the antiepileptic potential of phytoconstituents in the preclinical study (in-vitro, in-vivo) is provided based on their effect on screening parameters. Besides, relevant information on pharmacology of phytoconstituents, the traditional use of their medicinal plants related to epilepsy and status of phytoconstituents in the clinical study were derived from online databases, including PubMed, Clinicaltrial. gov, The Plant List (TPL, www.theplantlist.org), Science Direct. Articles identified using preset searching syntax and inclusion criteria are presented.
RESULTS: More than 70% of the phytoconstituents reviewed in this paper justified the traditional use of their medicinal plant related to epilepsy by primarily acting on the GABAergic system. Amongst the phytoconstituents, only cannabidiol and tetrahydrocannabinol have been explored for clinical application in epilepsy.
CONCLUSION: The preclinical and clinical data of the phytoconstituents to treat epilepsy and its associated comorbidities provides evidence for the discovery and development of novel antiepileptic drugs from medicinal plants. In terms of efficacy and safety, further randomized and controlled clinical studies are required to understand the complete pharmacodynamic and pharmacokinetic picture of phytoconstituents. Also, specific botanical source evaluation is needed.
AIM OF THE STUDY: To identify the mechanisms underlying protective effect of MPLA on the bone in estrogen-deficient, diabetic condition.
METHODS: Adult female, estrogen-deficient, diabetic rats (225 ± 10 g) were divided into untreated group and treated with M. pumilum leaf aqueous extract (MPLA) (50 mg/kg/day and 100 mg/kg/day) and estrogen for 28 days (n = 6 per group). Fasting blood glucose (FBG) levels were weekly monitored and at the end of treatment, rats were sacrificed and femur bones were harvested. Bone collagen distribution was observed by Masson's trichome staining. Levels of bone osteoblastogenesis, apoptosis and proliferative markers were evaluated by Realtime PCR, Western blotting, immunofluorescence and immunohistochemistry.
RESULTS: MPLA treatment was able to ameliorate the increased in FBG levels in estrogen deficient, diabetic rats. In these rats, decreased bone collagen content, expression level of osteoblastogenesis markers (Wnt3a, β-catenin, Frizzled, Dvl and LRP-5) and proliferative markers (PCNA and c-Myc) and increased expression of anti-osteoblastogenesis marker (Gsk-3β) and apoptosis markers (Caspase-3, Caspase-9 and Bax) but not Bcl-2 were ameliorated. Effects of 100 mg/kg/day MPLA were greater than estrogen.
CONCLUSION: MPLA was able to protect against bone loss, thus making it a promising agent for the treatment of osteoporosis in women with estrogen deficient, diabetic condition.
AIM OF THE REVIEW: This review aims to provide a comprehensive report on the ethnomedicinal use, phytochemistry, pharmacological activities, molecular mechanisms, and nutritional values of C. nutans. The present review will open new avenues for further in-depth pharmacological studies of C. nutans for it to be developed as a potential nutraceutical and to improve the available products in the market.
MATERIAL AND METHODS: All the available information on C. nutans was collected using the key words "Clinacanthus nutans" and/or "ethnomedicine" and/or "phytochemicals" and/or "anticancer" and/or "anti-inflammatory" and/or "antiviral" through an electronic search of the following databases: PubMed, Web of Science, EMBASE, Cochrane Library, Clinical Trials.org, SciFinder Scholar, Scopus, and Google Scholar. In addition, unpublished materials, Ph.D. and M.Sc. dissertations, conference papers, and ethnobotanical textbooks were used. The Plant List (www.theplantlist.org) and International Plant Name Index databases were used to validate the scientific name of the plant.
RESULTS: The literature supported the ethnomedicinal uses of C. nutans as recorded in Thailand, Indonesia, and Malaysia for various purposes. Bioactivities experimentally proven for C. nutans include cytotoxic, anticancer, antiviral, anti-inflammatory, immunomodulatory, antidiabetic, antioxidant, antihyperlipidemic, antimicrobial, and chemotherapeutic (in aquaculture) activities. Most of these activities have so far only been investigated in chemical, cell-based, and animal assays. Various groups of phytochemicals including five sulfur-containing glycosides, eight chlorophyll derivatives, nine cerebrosides, and a monoacylmonogalactosyl glycerol are present in C. nutans. The presence of two glycerolipids, four sulfur-containing compounds, six known flavones, a flavanol, four flavonols, two phytosterols, one polypeptide, and various phenolics and fatty acids largely influences its diverse bioactivities. Numerous reports justify the ethnomedicinal use of C. nutans as an antiviral agent in treating herpes simplex virus and varicella-zoster virus infections and as part of a traditional anticancer anti-inflammatory concoction agent for various inflammatory diseases. C. nutans tea was reported to have a good percentage of carbohydrate, crude protein, minerals, essential amino acids, nonessential amino acids, and essential fatty acids. Acute, subacute, and subchronic toxicity studies demonstrated that oral administration of ethanol and methanol extracts of C. nutans to male Swiss albino mice and male Sprague-Dawley (SD) rats, respectively, did not lead to any toxicity or adverse effects on the animal behavior and organs when used in amounts as high as 2g/kg.
CONCLUSION: The collected literatures demonstrated that, as an important traditional medicine, C. nutans is a promising ethnomedicinal plant with various extracts and bioactive compounds exhibiting multifarious bioactivities. However, it is important for future studies to conduct further in vitro and in vivo bioactivity evaluations systematically, following the standard pharmacology guidelines. It is crucial to elucidate in-depth molecular mechanisms, structure-activity relationships, and potential synergistic and antagonistic effects of multi-component extracts and bioactive constituents derived from C. nutans. Further studies should also focus on comprehensive toxicity that includes long-term effects and adverse effects on target organs of C. nutans and bioactive compounds in correlation with the specific pharmacological effects.