Potential use of barks of woody vascular plants in bone mending: A review.

The use of synthetic drugs to overcome bone ailments causes severe side effects, but the application of herbals is helpful in maintaining bone health and accelerating bone mending. Currently, there is no oral allopathic medicine to hasten bone healing, though folk and traditional practices have adopted herbal to fasten the recovery from bone ailments. Earliest recovery is a universally desired phenomenon, especially for elderly people where many more cases of traumatic injuries are common along the compromised body immunity. The computerized database search engines, such as Google Scholar, PubMed, ScienceDirect, Springer Link, etc., and textbooks were used to collect all relevant information about barks for bone mending activity published from 1990 onwards using certain keywords such as bark, folklore/ traditional bone healing practices, and phytopharmacology. The results obtained were compiled to make this review and related information is tabulated herewith. Traditional herbal bone healing exists in every society in the world. The plant barks of a few species (e.g., Ficus religiosa, Prunus cerasoides, Terminalia arjuna, etc.) have outstanding significance for bone healing because of their special chemical composition and novel properties to reduce swelling, pain, soreness, and speedy recovery of functions. Mostly bark extracts are rich in polyphenols, and minerals, represented with antioxidant, immunostimulatory, antibacterial properties, etc. There is a diversity of bark utilization for bone healing from different plant species, globally, of which only a few have been phytopharmacologically deciphered. Validated bark ingredients as medicine or food supplements are more useful due to the least side effects. Entrepreneurs have a scope to use bioactive obtained from plant barks that have not been scientifically screened till now. The research focused on the commercial application of plant barks as green medicine needs fingerprints of bioactive and clinically validated data including the concentration of biomarkers in the blood (IC50) for reducing the healing period. Phytopharmacological screening of barks used in folk medicine and synthesizing the therapeutics at mega quantities in industries is an array of hopes for sustainable utilization of natural resources. The bio-stimulating knowledge of certain herbal ingredients will be helpful in the development of synergistic formulations for rapid bone mending.

Relevance of Indian traditional tisanes in the management of type 2 diabetes mellitus: A review.

Background: Tisanes are a potential source of phytochemicals to reduce disease risk conditions and are used to protect from non-communicable diseases, globally. A few tisanes have gained more popularity than others depending on their chemical composition based on the geographical origin of the used herb. Several Indian tisanes have been claimed to have traits beneficial to people with or at a high risk of type 2 diabetes mellitus. Under the concept, the literature was reviewed and compiled into a document to highlight the chemical uniqueness of popular Indian traditional tisanes to be more informative and potent as per modern medicine to overcome type 2 diabetes mellitus. Methods: An extensive literature survey was conducted using computerized database search engines, such as Google Scholar, PubMed, ScienceDirect, and EMBASE (Excerpta Medica database) for herbs that have been described for hyperglycemia, and involved reaction mechanism, in-vivo studies as well as clinical efficacies published since 2001 onwards using certain keywords. Compiled survey data used to make this review and all findings on Indian traditional antidiabetic tisanes are tabulated here. Results: Tisanes render oxidative stress, counter the damage by overexposure of free radicals to the body, affect enzymatic activities, enhance insulin secretion, etc. The active molecules of tisanes also act as anti-allergic, antibacterial, anti-inflammatory, antioxidant, antithrombotic, antiviral, antimutagenicity, anti-carcinogenicity, antiaging effects, etc. WHO also has a strategy to capitalize on the use of herbals to keep populations healthy through effective and affordable alternative means with robust quality assurance and strict adherence to the product specification.

Gastroprotective mechanism of Paederia foetida Linn. (Rubiaceae)--a popular edible plant used by the tribal community of North-East India.

BACKGROUND: The objective of the present study is to evaluate the gastroprotective activity of Paederia foetida L. leaf for gastric ulcer. METHODS: The methanol extract of P. foetida L. leaves at two different dose levels was investigated for gastroprotective potential by using Indomethacin-pylorus ligation, alcohol induced and water immersion stress induced model in rats. In vitro DPPH* radical scavenging activity and western blot analysis of stomach tissue from pylorus ligatures rats were also carried out. HPTLC analysis was done to understand the phyto-pharmacological relationship. RESULTS: Methanol extract at a dose level of 100 mg/kg and 200 mg/kg body weight showed 72 and 78% ulcer protection when compared to negative control whereas reference drug shown 82% protection in Indomethacin-pylorus ligation model. Further, methanol extract also showed protective effect against 70% v/v ethanol and stress induced gastric ulcer model. About 84% protection as compared to cimetidine (85%) was seen in western blot analysis of stomach tissue from pylorus ligatures rats. HPTLC analysis of methanol extract of P. foetida L. confirmed the presence of ß-sitosterol. In DPPH* radical scavenging activity, the IC50 value was observed to be 43.52 µg/ml. CONCLUSIONS: These observations established the traditional claim and thus Paederia foetida could be a potent gastroprotective agent for use in future. The gastroprotective activity might be mediated by the Nrf2 mediated antioxidant and anti secretory effects.

Curcumin differs from tetrahydrocurcumin for molecular targets, signaling pathways and cellular responses.

Curcumin (diferuloylmethane), a golden pigment from turmeric, has been linked with antioxidant, anti-inflammatory, anticancer, antiviral, antibacterial, and antidiabetic properties. Most of the these activities have been assigned to methoxy, hydroxyl, α,ß-unsaturated carbonyl moiety or to diketone groups present in curcumin. One of the major metabolites of curcumin is tetrahydrocurcumin (THC), which lacks α,ß-unsaturated carbonyl moiety and is white in color. Whether THC is superior to curcumin on a molecular level is unclear and thus is the focus of this review. Various studies suggest that curcumin is a more potent antioxidant than THC; curcumin (but not THC) can bind and inhibit numerous targets including DNA (cytosine-5)-methyltransferase-1, heme oxygenase-1, Nrf2, ß-catenin, cyclooxygenase-2, NF-kappaB, inducible nitric oxide synthase, nitric oxide, amyloid plaques, reactive oxygen species, vascular endothelial growth factor, cyclin D1, glutathione, P300/CBP, 5-lipoxygenase, cytosolic phospholipase A2, prostaglandin E2, inhibitor of NF-kappaB kinase-1, -2, P38MAPK, p-Tau, tumor necrosis factor-α, forkhead box O3a, CRAC; curcumin can inhibit tumor cell growth and suppress cellular entry of viruses such as influenza A virus and hepatitis C virus much more effectively than THC; curcumin affects membrane mobility; and curcumin is also more effective than THC in suppressing phorbol-ester-induced tumor promotion. Other studies, however, suggest that THC is superior to curcumin for induction of GSH peroxidase, glutathione-S-transferase, NADPH: quinone reductase, and quenching of free radicals. Most studies have indicated that THC exhibits higher antioxidant activity, but curcumin exhibits both pro-oxidant and antioxidant properties.

Phytochemical mediated modulation of COX-3 and NFκB for the management and treatment of arthritis.

In this study, we investigated whether zerumbone (ZBN), ellagic acid (ELA) and quercetin (QCT), the plant-derived components, can modulate the role of COX-3 or cytokines liable in arthritic disorder. Initially, the effect of ZBN, ELA, and QCT on inflammatory process was investigated using in-vitro models. In-silico docking and molecular dynamics study of these molecules with respective targets also corroborate with in-vitro studies. Further, the in-vivo anti-arthritic potential of these molecules in Complete Freund's adjuvant (CFA)-induced arthritic rats was confirmed. CFA increases in TNF-α and IL-1ß levels in the arthritic control animals were significantly (***p < 0.001) attenuated in the ZBN- and ELA-treated animals. CFA-induced attenuation in IL-10 levels recovered under treatment. Moreover, ELA attenuated CFA-induced upregulation of COX-3 and ZBN downregulated CFA-triggered NFκB expression in arthritic animals. The bonding patterns of zerumbone in the catalytic sites of targets provide a useful hint in designing and developing suitable derivatives that can be used as a potential drug. To our best knowledge, the first time we are reporting the role of COX-3 in the treatment of arthritic disorders which could provide a novel therapeutic approach for the treatment of inflammatory disorders.

Correction: Calpain and Reactive Oxygen Species Targets Bax for Mitochondrial Permeabilisation and Caspase Activation in Zerumbone Induced Apoptosis.

[This corrects the article DOI: 10.1371/journal.pone.0059350.].

Antioxidant and hepatoprotective activity of ethanolic and aqueous extracts of Momordica dioica Roxb. leaves.

In present study, the hepatoprotective activity of ethanolic and aqueous extracts of Momordica dioica Roxb. leaves were evaluated against carbon tetrachloride (CCl4) induced hepatic damage in rats. The extracts at dose of 200mg/kg were administered orally once daily. The substantially elevated serum enzymatic levels of serum glutamate oxaloacetate transaminase (AST), serum glutamate pyruvate transaminase (ALT), serum alkaline phosphatase (SALP) and total bilirubin were restored towards normalization significantly by the extracts. Silymarin was used as standard reference and exhibited significant hepatoprotective activity against carbon tetrachloride induced haptotoxicity in rats. The biochemical observations were supplemented with histopathological examination of rat liver sections. The results of this study strongly indicate that Momordica dioica Roxb. leaves have potent hepatoprotective action against carbon tetrachloride induced hepatic damage in rats. Ethanolic extract was found more potent hepatoprotective. Meanwhile, in vivo antioxidant and free radical scavenging activities were also screened which were positive for both ethanolic and aqueous extracts. This study suggests that possible mechanism of this activity may be due to free radical-scavenging and antioxidant activities which may be due to the presence of flavonoids in the extracts.

Hepatoprotective Effect of Auricularia delicata (Agaricomycetes) from India in Rats: Biochemical and Histopathological Studies and Antimicrobial Activity.

Auricularia delicata, an edible mushroom, has been used as a traditional medicine in Manipur, India, for various gastrointestinal and liver ailments. This study evaluates the antioxidant, antimicrobial, and hepatoprotective potential of A. delicata. A. delicata fruiting bodies were extracted with hexane, chloroform, ethyl acetate, and methanol. All these extracts were examined for in vitro antioxidant activity. To study antimicrobial activity, minimum inhibitory concentrations (milligrams per milliliter) were determined through the use of the broth dilution method. In vivo hepatoprotective activity against acetaminophen-induced hepatic injury in rats was investigated by evaluating serum biochemistry, antioxidant enzymes, and histopathology. With regard to antioxidant activity, 21 and 48 µg/mL were the lowest half-maximal effective concentrations, obtained for the methanol and ethyl acetate fractions, respectively. In the antimicrobial study, the ethyl acetate fraction showed the lowest inhibition of Bacillus subtilis, Enterococcus feacium, Streptococcus aureus, B. cereus, and Escherichia coli, with minimum inhibitory concentrations of 0.03, 0.015, 0.03, 0.11, and 0.5 mg/mL, respectively. Further, in in vivo studies, elevated levels of biochemical markers were significantly returned to near normal values; this was supported by histopathological changes. Thus A. delicata showed antimicrobial, antioxidant, and protective roles in induced hepatic injury. Phytochemical analysis using high-performance liquid chromatography revealed the presence of chlorogenic acid in the extracts. Its protective property might be due to the presence of a mitochondrial-targeted antioxidant effect of chlorogenic acid. The antimicrobial activity accounts for its use against diarrhea. Hence, A. delicata could be one of the best sources for natural gastrointestinal and hepatoprotective medicines in the future.

Targeting Cell Survival Proteins for Cancer Cell Death.

Escaping from cell death is one of the adaptations that enable cancer cells to stave off anticancer therapies. The key players in avoiding apoptosis are collectively known as survival proteins. Survival proteins comprise the Bcl-2, inhibitor of apoptosis (IAP), and heat shock protein (HSP) families. The aberrant expression of these proteins is associated with a range of biological activities that promote cancer cell survival, proliferation, and resistance to therapy. Several therapeutic strategies that target survival proteins are based on mimicking BH3 domains or the IAP-binding motif or competing with ATP for the Hsp90 ATP-binding pocket. Alternative strategies, including use of nutraceuticals, transcriptional repression, and antisense oligonucleotides, provide options to target survival proteins. This review focuses on the role of survival proteins in chemoresistance and current therapeutic strategies in preclinical or clinical trials that target survival protein signaling pathways. Recent approaches to target survival proteins-including nutraceuticals, small-molecule inhibitors, peptides, and Bcl-2-specific mimetic are explored. Therapeutic inventions targeting survival proteins are promising strategies to inhibit cancer cell survival and chemoresistance. However, complete eradication of resistance is a distant dream. For a successful clinical outcome, pretreatment with novel survival protein inhibitors alone or in combination with conventional therapies holds great promise.

Past, present and perspectives of Manipur traditional medicine: A major health care system available for rural population in the North-East India.

BACKGROUND: Traditional health care practices are still being followed extensively in Manipur, North-East India. This is the major or the only medical facility available in some rural areas of Manipur. Cross cultural ethno-pharmacological survey was conducted to document traditional health care practices by Maiba-Maibi (male-female traditional health care practitioners of Manipur). MATERIALS AND METHODS: All together 59 traditional practitioners belonging to 12 ethnic communities in nine districts of the Manipur state were interviewed. A predesigned questionnaire was used for interviews, which included queries for type of ailments treating, symptoms, bioresources used, method of preparation, dosage forms, formulation, unit doses. The entire interviews were done in the residence of respective Maiba-Maibi, their patient handing and preparation of medicinal formulations were documented in written and audio-visual format. RESULTS: The survey recorded traditional knowledge on 949 formulations used for 66 human ailments. Five hundred forty six plant products, 42 animal products and 22 organic/inorganic materials were found to be used in these 949 formulations. Five plant species - Zingiber officinale (Zingiberaceae), Cocos nucifera (Arecaceae), Oroxylum indicum (Bignonaceae), Curcuma longa (Zingiberaceae) and Allium sativum (Liliaceae) used by maximum number of Maiba and Maibi in maximum number of formulations. RECOMMENDATION: This particular method of documentation keeps traditional knowledge alive. The WHO estimated perspective of traditional medicine across the world. These observations support therapeutic worth of Manipur Traditional medicines (MTM). Having generated a large database in course of this survey, next focus targeted for the scientific justification of MTM with an aim to develop commercially viable products.

Anti-diabetic potential of selected ethno-medicinal plants of north east India.

ETHNOPHARMACOLOGICAL RELEVANCE: Through one-to-one interaction with the traditional healers, the present study has identified 15 medicinal plant species traditionally used as remedies to control diabetes. MATERIALS AND METHODS: The methanolic extracts were screened for their α-glucosidase inhibitory activity. Hypoglycemic activity was assessed following glucose, sucrose and starch tolerance test on normal and STZ induced diabetic rats. RESULTS: Ficus cunia extract had the highest α-glucosidase inhibitory potency with IC50 1.39±0.74 µg mL(-1) followed by Schima wallichi (IC50 1.43±0.20 µg mL(-1)) and Wendlandia glabrata (IC50 1.67±0.33 µg mL(-1)). In STZ induced diabetic rat model, F. cunia and W glabrata extracts reduced blood glucose concentration to near normal up to 14 days when administered 48 h after STZ. CONCLUSION: The present study supports the traditional use of some of these medicinal plants in anti-diabetic remedies. The present study contributes to evidence for use of traditional medicine.

Development of an Efficient Virus Induced Gene Silencing Strategy in the Non-Model Wild Ginger-Zingiber zerumbet and Investigation of Associated Proteome Changes.

Zingiber zerumbet (Zingiberaceae) is a wild, tropical medicinal herb that shows a high degree of resistance to diseases affecting cultivated ginger. Barley stripe mosaic virus (BSMV) silencing vectors containing an endogenous phytoene desaturase (PDS) gene fragment were agroinfiltrated into young leaves of Z. zerumbet under controlled growth conditions to effect virus-induced gene silencing (VIGS). Infiltrated leaves as well as newly emerged leaves and tillers showed visual signs of PDS silencing after 30 days. Replication and systemic movement of the viral vectors in silenced plants were confirmed by RT-PCR. Real-time quantitative PCR analysis verified significant down-regulation of PDS transcripts in the silenced tissues. Label-free proteomic analysis was conducted in leaves with established PDS transcript down regulation and buffer-infiltrated (mock) leaves. A total of 474 proteins were obtained, which were up-regulated, down-regulated or modulated de novo during VIGS. Most of these proteins were localized to the chloroplast, as revealed by UniprotKB analysis, and among the up-regulated proteins there were abiotic stress responsive, photosynthetic, metabolic and membrane proteins. Moreover, the demonstration of viral proteins together with host proteins proved successful viral infection. We report for the first time the establishment of a high-throughput gene functional analysis platform using BSMV-mediated VIGS in Z. zerumbet, as well as proteomic changes associated with VIGS.

Antifertility efficacy of Drynaria quercifolia (L.) J. Smith on female Wister albino rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Plant based traditional medicines for birth control has been in practice in rural populations of North-East India, since time immemorial. Fresh rhizome of Drynaria quercifolia (L.) J. Smith is one of the plant parts used traditionally by different ethnic communities in Tripura, India for birth control. The present investigation is aimed to justify the scientific basis in traditional use of Drynaria quercifolia rhizome as anti-fertility agent. MATERIALS AND METHODS: Ex-vivo uterotonic activity was done on uterine tissue. Acute toxicity test of the plant extract was carried out in rats of both sexes. The abortifacient and anti-implantation activities of the extract were investigated, in-vivo and estimated the level of different hormones release. RESULTS: The result revealed the effectiveness of methanol (87%) and aqueous (68%) extract of the plant on uterotonic activity. The extracts showed relatively non-toxic effect in acute toxicity study. Methanolic extract has shown higher efficacy for both abortifacient (**p<0.01) and anti-implantation performance (**p<0.01) and also effected hormone release level (**p<0.01). CONCLUSION: Methanolic extract of Drynaria quercifolia (L.) J. Smith rhizome has been proved to have significant anti-fertility activity.

Protective effect of Clerodendrum colebrookianum Walp., on acute and chronic inflammation in rats.

AIM: To evaluate antioxidant, anti-inflammatory potential of the aqueous extracts and its aqueous, n-butanol, ethyl-acetate, and chloroform fractions of Clerodendrum colebrookianum Walp. leaves. MATERIALS AND METHODS: In this present study, all the test samples were evaluated on in-vivo inflammatory model such as carrageenan and histamine-induced acute-inflammation and cotton pellet induced granuloma formation in albino male rats. Test samples were also employed in in-vitro assays like DPPH free radical scavenging activity and COX inhibition assay. RESULTS: The test samples at the dose of 200mg/kg/p.o. were found to cause significant inhibition of carrageenan and histamine-induced inflammation and cotton pallet-induced granuloma formation on acute and chronic inflammation in rats. The test samples, except n-butanol fraction, exhibited inhibitory effect for both COX-1 and COX-2, in in-vitro assay but their percentage of inhibition values differs from each other. The test samples (aqueous extracts, aqueous, n-butanol, ethyl-acetate, and chloroform fractions) at 100 µg concentration exhibits 54.37%, 33.88%, 62.85%, 56.28%, and 57.48% DPPH radical-scavenging effect respectively in in-vitro antioxidant study. CONCLUSION: These observations established the anti-inflammatory effect of C. colebrookianum leaves in acute and chronic stages of inflammation by free radical scavenging and inhibition of COX-1 and COX-2.

In Vitro and In Vivo Evaluation of Polyherbal Formulation against Russell's Viper and Cobra Venom and Screening of Bioactive Components by Docking Studies.

The present study emphasizes to reveal the antivenom activity of Aristolochia bracteolata Lam., Tylophora indica (Burm.f.) Merrill, and Leucas aspera S. which were evaluated against venoms of Daboia russelli russelli (Russell's viper) and Naja naja (Indian cobra). The aqueous extracts of leaves and roots of the above-mentioned plants and their polyherbal (1 : 1 : 1) formulation at a dose of 200 mg/kg showed protection against envenomed mice with LD50 doses of 0.44 mg/kg and 0.28 mg/kg against Russell's viper and cobra venom, respectively. In in vitro antioxidant activities sample extracts showed free radical scavenging effects in dose dependent manner. Computational drug design and docking studies were carried out to predict the neutralizing principles of type I phospholipase A2 (PLA2) from Indian common krait venom. This confirmed that aristolochic acid and leucasin can neutralize type I PLA2 enzyme. Results suggest that these plants could serve as a source of natural antioxidants and common antidote for snake bite. However, further studies are needed to identify the lead molecule responsible for antidote activity.

Calpain and reactive oxygen species targets Bax for mitochondrial permeabilisation and caspase activation in zerumbone induced apoptosis.

Fluorescent protein based signaling probes are emerging as valuable tools to study cell signaling because of their ability to provide spatio- temporal information in non invasive live cell mode. Previously, multiple fluorescent protein probes were employed to characterize key events of apoptosis in diverse experimental systems. We have employed a live cell image based approach to visualize the key events of apoptosis signaling induced by zerumbone, the active principle from ginger Zingiber zerumbet, in cancer cells that enabled us to analyze prominent apoptotic changes in a hierarchical manner with temporal resolution. Our studies substantiate that mitochondrial permeabilisation and cytochrome c dependent caspase activation dominate in zerumbone induced cell death. Bax activation, the essential and early event of cell death, is independently activated by reactive oxygen species as well as calpains. Zerumbone failed to induce apoptosis or mitochondrial permeabilisation in Bax knockout cells and over-expression of Bax enhanced cell death induced by zerumbone confirming the essential role of Bax for mitochondrial permeabilsation. Simultaneous inhibition of reactive oxygen species and calpain is required for preventing Bax activation and cell death. However, apoptosis induced by zerumbone was prevented in Bcl 2 and Bcl-XL over-expressing cells, whereas more protection was afforded by Bcl 2 specifically targeted to endoplasmic reticulum. Even though zerumbone treatment down-regulated survival proteins such as XIAP, Survivin and Akt, it failed to affect the pro-apoptotic proteins such as PUMA and BIM. Multiple normal diploid cell lines were employed to address cytotoxic activity of zerumbone and, in general, mammary epithelial cells, endothelial progenitor cells and smooth muscle cells were relatively resistant to zerumbone induced cell death with lesser ROS accumulation than cancer cells.

Evaluation of anti-fertility activity of Tabernaemontana divaricata (Linn) R.Br. leaves in rats.

The aim of the present study was to assess the anti-fertility activity of ethanolic extracts of Tabernaemontana divaricata (TD) leaves in oestrogenic activity models in immature female rats. Mature green leaves of TD were collected and authenticated. Extractions of the dried leaves were carried out with ethanol in a Soxhlet's apparatus. For oestrogenic activity, the extracts were administered orally once daily at a dose of 200 and 400 mg kg(-1), and the activity was compared with the standard drug ethinyl oestradiol (0.02 mg). The extracts caused significant increase in uterine weight compared to the control. The ethanolic extract exhibited oestrogenic activity. The histological study of epithelium tissues with the 400 mg of TD extract-treated animals showed increases in the height of the luminal epithelium and loose edematous stroma when compared with the 200 mg of TD extract-treated group of animals. However, this was better than the control group of animals. Enhanced uterine weight and increase in the height of luminal epithelium and histological characteristics suggest that TD extract may be useful in anti-fertility therapy.