Design and synthesis of Aza-boeravinone derivatives as potential novel topoisomerase I inhibitors.

Based on the structural skeleton of natural products boeravinones, two types of 6H-chromeno[3,4-b]quinoline derivatives were designed and synthesized by nitrogen atom substitution strategy. Then, their cytotoxic activities were evaluated against six human tumor cell lines including HepG2 (hepatocellular carcinoma), A2780 (ovarian cancer), Hela (cervical cancer), HCT116 (colorectal cancer), SW1990 (pancreatic cancer), and MCF7 (breast cancer). The results showed that compounds ZML-8 and ZML-14 exhibited robust inhibitory activities against HepG2 cells with IC50 values of 0.58 and 1.94 µM, respectively. In addition, ZML-8 and ZML-14 showed higher selectivity against HepG2 and L-02 cells than Topotecan. Mechanistically, ZML-8 and ZML-14 not only induced cell cycle arrest in the G2/M phase and cell apoptosis, but also dose-dependently inhibited topoisomerase I activity and induced DNA damage in HepG2 cells. Molecular docking showed that ZML-8 and ZML-14 could interact with topoisomerase I-DNA complex with a similar binding mode to Topotecan. Inhibitory activities of these two compounds on topoisomerase I were then confirmed in both cell-free systems and in whole-cell lysates. Taken together, compounds ZML-8 and ZML-14 merit further development as a new generation of non-camptothecin topoisomerase I inhibitors for the treatment of cancer.

Boeravinone B alleviates gut dysbiosis during myocardial infarction-induced cardiotoxicity in rats.

Myocardial infarction (MI) is the most common heart disease, and also, it is one of the leading causes of death from cardiovascular disease. It is well known that MI causes additional injury during blood flow restoration in ischaemic myocardium. Boeravinone B (BB) is a well-known antioxidant and anti-inflammatory drug. We investigated the cardioprotective effect of BB drug against isoproterenol (ISO)-induced MI in rats in this experimental study, along with we analysed its underlying mechanism. Adult Sprague Dawley (SD) rats were treated subcutaneously with ISO (45 mg/kg), then divided into groups and then given BB drug was administered orally. The cardioprotective effect of BB on ISO-induced MI rats was analysed by estimating the heart injury markers, antioxidant pro-inflammatory cytokines and inflammatory parameters. We also detected quantified expression of inflammation and apoptosis-related marker protein family. We estimated the effect of BB drug on GUT microbiota in ISO-induced MI rats and scrutinized the histopathological variations in heart tissues. BB treatment significantly (P < .001) diminished the level of heart markers such as lactate dehydrogenase (LDH), troponin (TnT), creatine kinase (CK) and creatine kinase isoenzymes MB (CK-MB). BB treatment also altered the antioxidant parameters and reduced the pro-inflammatory cytokines in the serum and tissues. Additionally, the histopathological aspects demonstrated that the pathological changes observed in the heart tissue of the ISO group rats were suppressed by the BB treatment to varying degrees. Furthermore, the expressions of caspase-3, p53, caspase-9, Bax, interleukin-6 (IL-6), cytochrome C, neutrophil gelatinase-associated lipocalin (NGAL), tumour necrosis factor-α (TNF-α), nuclear factor kappa B (NF-κB) and interleukin-1ß (IL-1ß) in the heart tissue were down-regulated whereas the Bcl-2 expression seemed to be enhanced. BB treatment not only alleviated ISO-induced gut dysbiosis by its enhanced specified Firmicutesto-Bacteroidetes (F/B) ratio but also maintained the relative abundance of major bacteria such as Clostridium IV, Butyricicoccus, Clostridium XIVs, Akkermansia and Roseburia. Collectively, our findings showed that the BB drug acted against myocardial infraction and prevented the damage by reducing the oxidative stress and controlling the inflammatory pathways, and gut microbiota.

Anti-inflammatory potential of a lipid-based formulation of a rotenoid-rich fraction prepared from Boerhavia diffusa.

CONTEXT: Boerhavia diffusa L. (Nyctaginaceae) roots are used in Ayurveda for treating inflammatory diseases. Generally poor oral bioavailability is a major problem associated with herbal drugs. OBJECTIVE: To develop a phospholipid complex of rotenoid-rich fraction (RRF) and evaluate its in vivo anti-inflammatory activity and pharmacokinetic study. MATERIALS AND METHODS: RRF was prepared from a 70% ethanol extract of B. diffusa roots. This RRF was complexed with phosphatidylcholine by refluxing in 70% ethanol. In vivo anti-inflammatory activity of RRF-PC and RRF was determined using the carrageenan-induced rat paw edema method, at a dose equivalent to 100 mg/kg p.o. of RRF. Edema volume was calculated at 3 and 5 h. The plasma concentration of boeravinone B was estimated in rats at a same dose level. Blood samples were collected at 1, 2, 4, 6, 8, 10, 12, 24, and 36 h. RESULTS: (1)H and (31)P NMR spectra of RRF-PC showed up-field shift of protons of the (+)N(CH3)3 group (3.37 → 3.23) and the phosphorus atom (-1.26 → -1.57 ppm), respectively, which confirmed phospholipid complex formation between phosphatidylcholine [PO4 and (+)N(CH3)3 groups] and phytoconstituents by hydrogen bonding. The RRF-PC showed significantly enhanced in vivo anti-inflammatory activity (64%) as compared with RRF (48%) and ibuprofen (50%) at 5 h (p < 0.001). Furthermore, detected plasma concentration of boeravinone B was two times higher in RRF-PC (75 ng/mL) as compared with RRF (40 ng/mL). CONCLUSION: The present study demonstrated an increased anti-inflammatory potential and higher plasma level of boeravinone B in lipid-based formulation (RRF-PC) as compared with RRF.

Renal Protective Effect of Boeravinone B against Diabetic Nephropathy Rats via Inhibition of The Inflammatory and JAK2/STAT3 Signalling Pathway.

OBJECTIVE: Chronic inflammation is a common feature in diabetes, especially when blood sugar levels are poorly controlled. This chronic low-grade inflammation can affect various organs, including the kidneys. Podocyte damage play a key role in the development of diabetic nephropathy (DN). The aim of the study was to evaluate the nephroprotective effect of Boeravinone B (BB) against streptozotocin (STZ) induced DN in rats and explore the underlying mechanism. MATERIALS AND METHODS: In this experimental study, the rats received intraperitoneal injections of STZ (60 mg/kg) to induce DN. Various doses of BB (2.5, 5, and 7.5 mg/kg) were administered orally. Glucose levels, body weights, and organ weights (hepatic and renal) were assessed. Renal, histomorphological, antioxidant, hepatic, and cytokine levels were determined, as were the mRNA expression levels of JAK2 and STAT3. At end of the experimental study, the rats were sacrificed and their renal tissues were removed for histopathological assessment. RESULTS: BB treatment decreased glucose levels and increased body weights. This treatment suppressed hepatic weights, increased renal tissue weights, and also decreased renal parameters like uric acid, urea, bilirubin, creatinine (Cr) and, albumin. There was a decrease (P<0.001) in histomorphological parameters such as kidney hypertrophy index (KHI), mean glomerular volume (MGV), foot process fusion ratio (FPFR), and glomerular basement membrane thickness (GBMT) after treatment with BB. In addition, this treatment improved the levels of renal podocin, renal CD2- associated protein (CD2AP) and suppressed hepatic parameter levels. BB treatment (P<0.001) altered antioxidant parameters and cytokine levels, and suppressed mRNA expressions of JAK2, STAT3, RAGE, KIM-1, NAGL, and S100A8. CONCLUSION: Administration of BB showed renal protective effects against STZ-induced DN in rats via the reduction of oxidative stress and inflammatory reactions.

Two new phenolic compounds from Boerhavia erecta collected in Vietnam.

Boerhavia erecta is a tropical plant that is widely used in Asian folk medicine. Little is known about the alpha-glucosidase inhibition and antimicrobial properties of compounds from this plant. In the present study, the phytochemical study of the aerial parts of B. erecta collected in Vietnam was conducted using multiple chromatographic methods. The chemical structures of isolated compounds were identified by comprehensive spectroscopic methods. Two new compounds, berectone C (1) and (E)-tetracosyl 3-(3-hydroxy-4-methoxyphenyl)acrylate (4), together with the known compounds boeravinone C (2), liquiritigenin (3), bis(1H-indol-3-yl)methanone (5), and indole-3-carboxylic acid (6) were isolated and structural elucidated. Compounds 1 and 4 were evaluated for alpha-glucosidase inhibition and antimicrobial activity against antibiotic-resistant, pathogenic bacteria Enterococcus faecium, Staphylococcus aureus, and Acinetobacter baumannii. Compound 1 showed strong inhibition of the alpha-glucosidase enzyme (IC50 43 µg/mL). Only compound 1 exhibited antimicrobial property against A. baumannii, forming an inhibition zone of 11 mm.

Chemoprotective effect of boeravinone B against 1,2-dimethyl hydrazine induced colorectal cancer in rats via suppression of oxidative stress and inflammatory reaction.

Background: Colorectal cancer (CRC) has few or no symptoms and is often diagnosed at its end stage. Boeravinone B (BB) is a natural rotenoid which induces an antioxidative effect and has been used in cancer prevention. In this study, we scrutinized the chemoprotective effect of BB against 1,2dimethyl hydrazine (DMH) induced CRC in rats. Methods: Subcutaneous administration of DMH (40 mg/kg) was used for the induction of CRC in rats, followed by oral administration of BB. The body weight, tumor volume, tumor incidence, and total number of tumors were estimated in all rat groups rats except the normal group. Antioxidant parameters, phase I and II enzymes, and inflammatory cytokines and parameters were estimated at the completion of the study. Results: DMH induced group rats exhibited a tumor incidence of 100% along with several tumors/polyps per tumor­bearing rat, while BB treatment remarkably suppressed the incidence of tumors and suppressed polyps per tumor bearing rat. BB treatment significantly (P<0.001) altered the level of antioxidant parameters, phase I and phase II enzymes, and cytokines such as TNF-α, IL-1ß, IL-4, IL-6, and IL-10, and treatment significantly (P<0.001) suppressed the level of inflammatory cytokines, including cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), and inducible nitric oxide synthase (iNOS). Conclusions: BB treatment considerably suppresses colon cancer via its antioxidant and anti-inflammatory mechanism.

Anti-Obesity Action of Boerhavia diffusa in Rats against High-Fat Diet-Induced Obesity by Blocking the Cannabinoid Receptors.

Obesity, type 2 diabetes, and cardiovascular illnesses have known risk factors in the pathophysiology of an unhealthy diet. Obesity now affects almost a third of the world's population and is widely seen as a side effect of the Industrial Revolution. The current study aimed to determine natural phytoconstituents that have a significant role in the management of obesity. In this view, we have selected the plant Boerhavia diffusa which has different pharmacological actions and is traditionally used to treat sickness caused by lifestyle modification. The methanolic extract of the plant material was prepared and then further fractionated by means of solvents (n-hexane, chloroform, n-butanol, and water). The absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis was done by taking the active constituent of the plant (Punarnavine, Boeravinone B, and Eupalitin). The molecular docking analysis of these compounds is also performed by targeting the cannabinoid receptor (CR). Structural analysis of the best complex was done using the Discovery Studio visualizer tool. High-performance thin-layer chromatography (HPTLC) analysis was done by using a solvent system (chloroform and methanol in a ratio of 8:2). The in vivo study was done on the Sprague-Dawley (SD) rats treated with a high-fat diet to induce obesity and different parameters such as body weight, behavioral activity, organ fat pad weight, lipid profile, and liver biomarkers (AST, ALT, BUN, and creatinine) were estimated. The result of the study suggested that the phytoconstituents of B. diffusa upon molecular docking revealed the possible binding mechanisms with the CR and thus show potent anti-obesity action.

Boeravinone B Protects Brain against Cerebral Ichemia Reperfusion Injury in Rats: Possible Role of Anti-inflammatory and Antioxidant.

It is well known that inflammatory reactions and oxidative stress play a key role in the pathogenesis of cerebral ischemia and secondary injury. Boeravinone B (BB) proofed their anti-inflammatory and antioxidant effect, but their neuroprotective effects still unknown. In this experimental study, we explore the neuro-protective effect of Boeravinone B on the ischemia/reperfusion and explore the possible mechanism. Male Wistar rats were used for the current experimental study. First induces natural I/R injury in rats and treated with BB and nifedipine, respectively. Rats were subjected to ischemia after 6 consecutive days by occlusion of the bilateral common carotid arteries (BCCAO). Neurological score, biochemical, antioxidant, pro-inflammatory cytokines and inflammatory parameters were estimated in the serum and brain tissue. BB treatment significantly (p < 0.001) suppressed neuronal injury, dose-dependently decreased the cerebral water content. BB treatment altered the pro-inflammatory cytokines, antioxidant and inflammatory mediators in the serum and brain tissue. BB regulated the expression of glycine (Gly), glutamic acid (Glu), taurine (Tau), aspartic acid (Asp) and γ-aminobutyric acid (GABA) and enhanced the activity of Na+, K+ ATPase and Ca2+ ATPase. BB significantly (p < 0.001) reduced antioxidant enzymes such as glutathione (GSH), glutathione peroxidase (GPx), catalase (CAT), malondialdehyde (MDA), glutathione reductase (GR); inflammatory cytokines include interleukin-4 (IL-4), interleukin-1 (IL-1), tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), interleukin-6 (IL-6) and interleukin-1ß (IL-1ß); inflammatory mediators include prostaglandin (PGE2), nuclear kappa factor B (NF-κB) and cyclooxygenase-2 (COX-2), respectively. In this study, we have found that Boeravinone B exhibited protection against cerebral I/R by reducing oxidative stress and inflammatory reaction.

A Review on Rotenoids: Purification, Characterization and its Biological Applications.

Phytochemicals play a vital role as drugs for the treatment of various autoimmune, viral, and cancerous diseases. Rotenoids, a type of isoflavone compounds present in plants genus Boerhaavia sp., Mirabilis sp. and Abronia sp. which belong to the Nyctaginaceae family, are traditionally used as pesticides and insecticides. Boeravinones are groups of rotenoid compounds widely used as drugs or drug adjuvants for the treatment of various diseases. Extraction of rotenoids in various solvents, purification of rotenoids in various chromatographic technique studies, and the characterization of functional groups of rotenoids in various spectroscopic techniques have been reported. Biological applications of rotenoids such as anti-cancerous, antioxidant, anti-inflammatory, antimicrobial, and cytotoxic activities have been discussed. This review summarizes the extraction, isolation, purification, and characterization of rotenoid compounds and their effect on the treatment of cancer, inflammatory, spasmolytic, autoimmune, and microbial diseases.

Chemoprotective Effect of Boeravinone B against DMBA/Croton Oil Induced Skin Cancer via Reduction of Inflammation.

Inflammatory reactions and oxidative stress play a major role in cancer expansion. Boeravinone B (BB) had already proofed their anti-inflammatory and antioxidant effects against various animal models of disease. In this experimental research, the chemoprotective effect of BB against skin cancer caused by 7,12-dimethylbenz(a)anthracene (DMBA)/croton oil was investigated and the possible mechanism was explored. Swiss albino mice were used in the current protocol. 100 µg/100 mL acetone, DMBA was used for induction the skin cancer and, after the 2-week repeated dose of croton oil (1% in acetone) give to the mice till end of the protocol. The mice were received the oral dose of BB (1.25, 2.5 and 5 mg/kg, body weight). The body weight and tumor incidence were estimated at regular time interval. At the end of the protocol, the antioxidant, phase I, phase II, pro-inflammatory cytokines and inflammatory mediators were scrutinized. The mRNA expression of pro-inflammatory cytokines and inflammatory mediators were estimated. BB treatment significantly (p < 0.001) reduced tumor incidence, tumor yield, average latency period and tumor burden in a dose-dependent manner. BB treatment considerably (p < 0.001) reduced the levels of lipid peroxidation (LPO) and increased the level of superoxide dismutase (SOD), glutathione (GSH), glutathione peroxidase (GPx), catalase (CAT) in DMBA/croton-induced skin cancer. BB treatment significantly (p < 0.001) reduced the level of phase I and phase II enzymes. BB treatment considerably reduced the cytokines include tumor necrosis factor-α (TNF-α), interleukin-18 (IL-18), interleukin-1ß (IL-1ß), interleukin-6 (IL-6) and inflammatory parameters such as transforming growth factor beta 1 (TGF-ß1), prostaglandin E2 (PGE2), nuclear kappa B factor (NF-κB) and cycloxgenase-2 (COX-2) in DMBA/croton-induced skin cancer mice. BB considerably (p < 0.001) reduced the mRNA expression of pro-inflammatory cytokines and inflammatory mediators. The results of the current investigation suggest that oral administration of boeravinone B significantly reduced skin cancer in mice via reduction of inflammatory reaction.

ß-Secretase inhibition by C-methylisoflavones from Abronia nana.

The methanol extract of Abronia nana suspension cultures were subjected to column chromatography to identify potential inhibitors of ß-secretase, which is a major factor in Alzheimer's disease development. Two new C-methylisoflavones boeravinone T (1) and U (4) were isolated with three knowns boeravinone B (2), J (3) and X (5). The half-maximal inhibitory concentration (IC50) values of compounds 1-5 were 18.29, 8.57, 7.87, 12.02 and 5.30 µM, respectively. The most potent 5, non-competitively inhibited ß-secretase [inhibition constant (Ki) = 3.79 µM]. Compounds 1-5 did not inhibit other proteases such as chymotrypsin, trypsin and elastase at concentrations up to 1 mM, indicating that they were relatively specific inhibitors of ß-secretase. A free hydroxyl group at C-3 position of the C-methylisoflavone skeleton appeared to be responsible for the stronger inhibitory activity against ß-secretase.

Chebulinic acid and Boeravinone B act as anti-aging and anti-apoptosis phyto-molecules during oxidative stress.

INTRODUCTION: Aquatic pollutant Malachite green (MG) induces oxidative stress by producing intracellular H2O2 and associated hydroxyl, hydroxymethyl or hydroperoxide radicals in Saccharomyces cerevisiae. These radicals disturb cellular functions leading to early aging. Exogenous supply of natural antioxidants may play a crucial role as anti-aging by ensuring the cellular survival. METHODS: Protective effect of Chebulinic acid (CA) and Boeravinone B (BB) was biochemically evaluated by measuring the expression levels of antioxidant enzymes. Intracellular oxidants generation, nuclear damage, necrosis, apoptosis, reduction in caspase 3/7 activity studied microscopically, spectrofluorometrically and biochemically along with growth dynamics and relative quantitation of Yap1, Sir2 and Bir1 expression using RT-PCR. RESULTS: Malachite green (MG) showed adverse effect on S. cerevisiae showing 400.83% enhancement in accumulation of intracellular H2O2 and associated hydroxyl, hydroxymethyl or hydroperoxide radicals. Independent supplementation of CA (5 µg/ml) and BB (3 µg/ml) significantly reduced the accumulation by 385.78 and 372.68%, respectively. Presence of MG extended the lag phase of growth curve and also reduced colony forming units (CFUs)/ml to 3 × 108 from 15 × 108. Whereas, CA and BB maintained the normal growth curve, CFUs and proved as anti-aging. Elevation in the activities of catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) by 241.35, 539.02 and 432.60% was observed after 2 h MG exposure. However, CA and BB significantly reduced the CAT, SOD and GPx activities. Microscopic observation of CA and BB augmented cells revealed protection from H2O2 and associated hydroxyl, hydroxymethyl or hydroperoxide radicals accumulation, nuclear disorganization, morphological distortion, apoptosis and necrosis contrary to MG exposed cells. An enhancement of 112.78% in caspase 3/7 activity was noted in MG exposed cells over control. Both CA and BB supplementation reduced the caspase 3/7 activity by 106.06 and 105.82%, respectively which was almost near normal. MG was found to induce the expression of yeast transcription factor Yap1; while presence of CA and BB restored expression of Yap1. Expression of longevity responsible gene Silent Information Regulator (Sir2) was also found to be reduced during MG exposure. However, CA and BB triggered the expression of Sir2. Similarly, MG lowered the expression of Baculoviral IAP repeat (Bir1) which is the inhibitor of apoptosis while CA and BB aided the over expression of Bir1. CONCLUSIONS: CA and BB supplementation could significantly decrease oxidative stress, enhance cell viability and ultimately protected S. cerevisiae cells form aging.

Boeravinone B a natural rotenoid exerts anticancer activity via inducing internalization and degradation of inactivated EGFR and ErbB2 in human colon cancer cells.

BACKGROUND: Epidermal growth factor receptors (EGFR) are identified to be favorable targets for cancer treatment. In present work, we showed that Boeravinone B, a Rotenoid from natural origin has significant anticancer activity via internalization of ErbB2 and EGFR, and thereby resulting in destruction of the receptors. METHODS: For cell viability and apoptosis were done by MTT assay. Annexin V-FITC staining was done for determining the extent of apoptosis. Immunoblotting for expression of proteins in HT-29 cell lysates after exposing them to Boeravinone G. Immunofluorescence and Confocal microscopic analysis was done for HT-29 cells incubated with anti-EGFR or anti-ErbB2 antibodies. Surface biotinylation assay was done followed by western blot analysis for expression of proteins using antibodies against transferrin receptor, ErbB2 and EGFR. RESULTS: Exposure of HT-29 cells with Boeravinone B suppressed constitutive as well as ligand mediated phosphorylation of ErbB2, ErbB3 and EGFR. The treatment also inhibited the activation of mitogen-activated protein kinase (MAPK), Akt and Erk1/2 which are downstream signaling molecules. The treatment also bought about internalization of ErbB2 and EGFR causing destruction of receptors, Boeravinone B also caused apoptosis in HT-29 cells. Boeravinone B mediated degradation was halted by Chloroquine (lysosomal inhibitor). Boeravinone B caused nuclear translocation of apoptosis-inducing factor (AIF) and caused proteolytic processing of PARP along with caspase-3, confirming Boeravinone B may induce caspase-independent apoptosis in HT-29 cells. CONCLUSION: The findings of present study provide first ever evidences for Boeravinone B suggesting anticancer activity via internalization and destruction of EGFR family receptors i.e. ErbB2 and EGFR in HT-29 cell lines.

Age-induced diminution of free radicals by Boeravinone B in Caenorhabditis elegans.

Oxidative damage is accrual of molecular deterioration from reactive oxygen species (ROS) while decrease in generation of ROS is related with free radical scavenging enzymes. Boerhaavia diffusa L. (Nyctaginaceae) derived novel molecule Boeravinone B (BOB) possesses a variety of pharmacological activities, yet their anti-aging potential has not been explored. The aim of the present study was to elucidate the mechanism of BOB mediated oxidative stress resistance and lifespan extension in Caenorhabditis elegans. The results showed that the BOB significantly extends the lifespan of C. elegans with its anti-oxidative potential via reducing accumulation of reactive oxygen species (ROS). BOB was found to recover the shortened lifespan of oxidative stress prone mutants mev-1 and gas-1 (14.75 and 16.11%, respectively). Additionally, this finding supported by the reduced ROS levels seen in BOB treated worms. Further, the effective concentration of BOB (25 µM) significantly enhanced the expressions of target genes such as superoxide dismutase (SOD-3), glutathione-S-transferase (GST-4) and heat shock protein (HSP-16.2) fused to green fluorescent protein (GFP), and it does so by modulating the stress-related signaling pathways (SEK-1) and transcription factors (SKN-1/Nrf and DAF-16/Foxo). Moreover, BOB exposure (25 µM) caused significant changes of age-dependent biomarkers such as pharyngeal pumping, body bend, locomotor activity and lipofuscin accumulation were also showed that BOB retards the aging. Overall, the findings highlight the antioxidant supplement triggering pharmaceutical potential of BOB which may serve as a new future perspective for healthy aging or delayed onset of oxidative related diseases.

Anti-HIV activity of southern African plants: Current developments, phytochemistry and future research.

ETHNOPHARMACOLOGICAL RELEVANCE: The African continent is home to a large number of higher plant species used over centuries for many applications, which include treating and managing diseases such as HIV. Due to the overwhelming prevalence and incidence rates of HIV, especially in sub-Saharan Africa, it is necessary to develop new and affordable treatments. AIM OF THE STUDY: The article provides an extensive overview of the status on investigation of plants from the southern African region with ethnobotanical use for treating HIV or HIV-related symptoms, or the management of HIV. The review also provide an account of the in vitro assays, anti-viral activity and phytochemistry of these plants. MATERIALS AND METHODS: Peer-reviewed articles investigating plants with ethnobotanical information for the treatment or management of HIV or HIV-related symptoms from the southern African region were acquired from Science Direct, PubMed central and Google Scholar. The selection criteria was that (1) plants should have a record of traditional/popular use for infectious or viral diseases, HIV treatment or symptoms similar to HIV infection, (2) if not traditionally/popularly used, plants should be closely related to plants with popular use and HIV activity identified by means of in vitro assays, (3) plants should have been identified scientifically, (4) should be native to southern African region and (5) anti-HIV activity should be within acceptable ranges. RESULTS: Many plants in Africa and specifically the southern African region have been used for the treatment of HIV or HIV related symptoms and have been investigated suing various in vitro techniques. In vitro assays using HIV enzymes such as reverse transcriptase (RT), integrase (IN) and protease (PR), proteins or cell-based assays have been employed to validate the use of these plants with occasional indication of the selectivity index (SI) or therapeutic index (TI), with only one study, that progressed to in vivo testing. The compounds identified from plants from southern Africa is similar to compounds identified from other regions of the world, and the compounds have been divided into three groups namely (1) flavonoids and flavonoid glycosides, (2) terpenoids and terpenoid glycosides and (3) phenolic acids and their conjugated forms. CONCLUSIONS: An investigation of the plants from southern Africa with ethnobotanical use for the treatment of HIV, management of HIV or HIV-related symptoms, therefore provide a very good analysis of the major assays employed and the anti-viral compounds and compound groups identified. The similarity in identified anti-viral compounds worldwide should support the progression from in vitro studies to in vivo testing in development of affordable and effective anti-HIV agents for countries with high infection and mortality rates due to HIV/AIDS.

Ethnomedicinal uses, phytochemistry and pharmacological properties of the genus Boerhavia.

ETHNOPHARMACOLOGICAL RELEVANCE: The genus Boerhavia is widely distributed in tropical, subtropical and temperate regions of the world including Mexico, America, Africa, Asia, Indian Ocean Islands, Pacific Islands and Australia. The genus Boerhavia is extensively used by local peoples and medicinal practitioners for treatments of hepatitis, urinary disorders, gastro intestinal diseases, inflammations, skin problems, infectious diseases and asthma. Present review focused on traditional uses, phytochemistry, pharmacology and toxicology of Boerhavia genus to support potential scope for advance ethnopharmacological study. MATERIALS AND METHODS: Information on the Boerhavia species was collected from classical books on medicinal plants, pharmacopoeias and scientific databases like PubMed, Scopus, GoogleScholar, Web of Science and others. Also scientific literatures based on ethnomedicinal surveys, Ph.D. and M.Sc. dissertations, published papers from Elsevier, Taylor and Francis, Springer, ACS as well as Wiley publishers and reports by government bodies and documentations were assessed. RESULTS: A total of 180 compounds from Boerhavia genus were isolated of which B. diffusa alone shared around 131 compounds and for most of which it is currently an exclusive source. In the genus, phenolic glycosides and flavonoids contribute approximately 97 compounds. These includes eupalitin, rotenoids like boeravinones, coccineons, alkaloid i.e. betanin and punarnavine etc., showing vital pharmaceutical activities such as anticancer, anti-inflammatory, antioxidant and immunomodulatory. CONCLUSION: Boerhavia is an important genus with wide range of medicinal uses. However, most of the available scientific literatures have lacked relevant doses, duration and positive controls for examining bioefficacy of extracts and its active compounds. In some studies, taxonomic errors were encountered. Moreover, there is need for accurate methods in testing the safety and ethnomedicinal validity of Boerhavia species.

Mirabijalone E: a novel rotenoid from Mirabilis himalaica inhibited A549 cell growth in vitro and in vivo.

ETHNOPHARMACOLOGICAL RELEVANCE: The roots of Mirabilis himalaica have been used in Tibetan folk medicine for treatment of uterine cancer, nephritis edematous, renal calculus and arthrodynia. In our previous work, the ethanol extract of roots had shown potent cytotoxicity against human cancer cells. However, no information is available on the antitumor effect of Mirabilis himalaica. The aim of the present study was to investigate the active constituents guided by bioassay and evaluate the related antitumor efficacy in vitro and in vivo. MATERIALS AND METHODS: The active subextract (ethyl acetate) was subjected to successive chemical separation using a combination of silica gel, LH-20 chromatography and semi-preparative HPLC. The structures were determined by spectroscopic analysis techniques such as nuclear magnetic resonance (NMR) and mass spectrometry. Three human cancer cell lines, A549, HepG2 and HeLa were used for in vitro cytotoxicity evaluation of all isolated compounds by MTT-assay. Then, the potent and novel compound mirabijalone E was employed to the mechanism study againstA549 cells. BrdU immunofluorescence, soft agar assay and cell cycle analysis were employed to detect the cell proliferation effects. Annexin V-FITC/PI staining assay was used for examining apoptotic effects. Expression levels of apoptosis-related proteins were determined by western blot assay. in vivo tumorigenic assay was used to evaluate the xenograft tumor growth treated with mirabijalone E. RESULTS: One new rotenoid compound, mirabijalone E, together with eight known rotenoids was isolated from Mirabilis himalaica. Mirabijalone E, 9-O-methyl-inone B, boeravinone C and boeravinone H exhibited cytotoxicity against A 549 and HeLa cells. Further study on mirabijalone E was carried out in vitro and in vivo. Mirabijalone E inhibited A549 cells growth in a time and dose-dependent manner, which arrested cell cycle in S phase. Mechanistically, mirabijalone E treatment resulted in the increase of Bax expression level, the decrease of Bcl-2 level and the activation of caspase-3, which suggested the activation of apoptosis cascades. Consequently, the xenograft treated with mirabijalone E showed markedly suppressed tumor growth. CONCLUSIONS: The result suggested that mirabijalone E, together with active compounds, 9-O-methyl-4-hydroxyboeravinone B, boeravinone C and boeravinone H could be a promising candidate for cancer therapy.