Antiproliferative Activity of Buddleja saligna (Willd.) against Melanoma and In Vivo Modulation of Angiogenesis.

Melanoma cells secrete pro-angiogenic factors, which stimulates growth, proliferation and metastasis, and therefore are key therapeutic targets. Buddleja saligna (BS), and an isolated triterpenoid mixture (DT-BS-01) showed a fifty percent inhibitory concentration (IC50) of 33.80 ± 1.02 and 5.45 ± 0.19 µg/mL, respectively, against melanoma cells (UCT-MEL-1) with selectivity index (SI) values of 1.64 and 5.06 compared to keratinocytes (HaCat). Cyclooxygenase-2 (COX-2) inhibition was observed with IC50 values of 35.06 ± 2.96 (BS) and 26.40 ± 4.19 µg/mL (DT-BS-01). BS (30 µg/mL) significantly inhibited interleukin (IL)-6 (83.26 ± 17.60%) and IL-8 (100 ± 0.2%) production, whereas DT-BS-01 (5 µg/mL) showed 51.07 ± 2.83 (IL-6) and 0 ± 6.7% (IL-8) inhibition. Significant vascular endothelial growth factor (VEGF) inhibition, by 15.84 ± 4.54 and 12.21 ± 3.48%, respectively, was observed. In the ex ovo chick embryo yolk sac membrane assay (YSM), BS (15 µg/egg) significantly reduced new blood vessel formation, with 53.34 ± 11.64% newly formed vessels. Silver and palladium BS nanoparticles displayed noteworthy SI values. This is the first report on the significant anti-angiogenic activity of BS and DT-BS-01 and should be considered for preclinical trials as there are currently no US Food and Drug Administration (FDA) approved drugs to inhibit angiogenesis in melanoma.

Human disorders associated with inflammation and the evolving role of natural products to overcome.

Inflammation is a biological function which triggered after the mechanical tissue disruption or from the responses by the incidence of physical, chemical or biological negotiator in body. These responses are essential act provided by the immune system during infection and tissue injury to maintain normal tissue homeostasis. Inflammation is a quite complicated process at molecular level with the involvement of several proinflammatory expressions. Several health problems are associated with prolonged inflammation, which effects nearly all major to minor diseases. The molecular and epidemiological studies jagged that the inflammation is closely associated with several disorders with their specific targets. It would be great achievement for human health around the world to overcome on inflammation. Mostly used anti-inflammatory drugs are at high risk of side effects and also expensive. Hence, the plant-based formulations gained a wide acceptance by the public and medical experts to treat it. Due to extensive dispersal, chemical diversity and systematically established biological potentials of natural products have induced renewed awareness as a gifted source for medications. However, today's urgent need to search for cheaper, more potent and safe anti-inflammatory medications to overcome on current situation. The goal of this review to compile an update on inflammation, associated diseases, molecular targets, inflammatory mediators and role of natural products. The entire text concise the involvement of various cytokines in pathogenesis of various human disorders. This assignment discussed about 321 natural products with their promising anti-inflammatory potential discovered during January 2009 to December 2018 with 262 citations.

Isolation of Flavonoids and Flavonoid Glycosides from Myrsine africana and Their Inhibitory Activities against Mushroom Tyrosinase.

Bioassay-guided fractionation of the methanol extract of the shoots of Myrsine africana led to the isolation of the new compound myricetin 3-O-(2″,4″-di-O-acetyl)-α-l-rhamnopyranoside (9) and 11 known compounds. The known compounds quercetin 3-O-(3″,4″-di-O-acetyl)-α-l-rhamnopyranoside (8), rutin (10), quercetin 3-O-α-l-rhamnopyranoside (11), and myricetin 3-O-α-l-rhamnopyranoside (12) are reported for the first time from the methanol extract of the shoots of M. africana. Compounds 10 and 12 showed significant inhibition of tyrosinase with 50% inhibition (IC50 values) of the enzyme at 0.13 ± 0.003 and 0.12 ± 0.002 mM, respectively, which was supported by the docking fitness scores obtained through molecular docking analysis. In addition, compounds 1-12 displayed significant antioxidant activity with IC50 values ranging 1.90 to 3.90 µM.

In vitro and In vivo Activity of Myrsine africana on Elastase Inhibition and Anti-wrinkle Activity.

BACKGROUND: Myrsine africana (MA) is a plant traditionally used in South Africa to treat various diseases. OBJECTIVE: The ethanolic extract of MA, was used for in vitro and in vivo studies to determine its elastase inhibitory activity. MATERIALS AND METHODS: MA and its isolated compound, myrsinoside B, were tested in vitro for their elastase inhibitory activity. The MA extract was also evaluated for mutagenicity using two strains of Salmonella typhimurium (TA 98 and TA 100), microbial count, metal analysis, and stability. In vivo studies included irritancy and wrinkle reduction trials using Visioscan and Visioface. RESULTS: The leaf extract showed good elastase inhibition with a 50% inhibitory concentration (IC50) of 28.04 µg/ml. Myrsinoside B inhibited the elastase enzyme at an IC50 of 4.68 ± 0.34 µg/ml. No colony growth observed during mutagenicity studies and it was concluded that MA ethanolic extract is a nonmutagen. MA extract was found to be a nonirritant during the patch test clinical trial. MA was found to contain negligible amounts of microorganisms and heavy metals. Gel cream containing MA crude extract was found to be stable for 2 years when kept at temperatures below 30°C. In clinical trials (in vivo), it was found that the test product containing 5% ethanolic extract of MA was effective in reducing wrinkles after application 2 times a day for 14 days and 28 days compared to the placebo aqueous cream. CONCLUSION: MA is effective in reducing the appearance of wrinkles. SUMMARY: This is a first time report of the elastase inhibitory potential of Myrsine africana and myrsinoside B and the anti-wrinkle potential of Myrsine africanaMyrsine africana ethanolic extract effectively inhibited the elastase enzymeMyrsine africana was effective in in vivo studies to reduce the appearance of wrinkles after 14 days. Abbreviations used: 4-NQO: 4-nitroquinoline, D14-BL: Baseline to day fourteen, D28-BL: Baseline to day twenty-eight, CFU: Colony forming units, IC50: 50% inhibitory concentration, MA: Myrsine africana, MOU: Measurement of uncertainty, NaCl: Sodium chloride, NaH2 PO4.H2O: Sodium phosphate monobasic monohydrate, SEM: Standard error of the mean, TA 98: Salmonella typhimurium strain 98, TA 100: S. typhimurium strain 100, TLC: Thin layer chromatography, TMA: Total microbial activity, XVB salt: Vogel-Bonner medium E.

Drug development against tuberculosis: Impact of alkaloids.

Despite of the advances made in the treatment and management, tuberculosis (TB) still remains one of main public health problem. The contrary effects of first and second-line anti-tuberculosis drugs have generated extended research interest in natural products in the hope of devising new antitubercular leads. Interestingly, plethoras of natural products have been discovered to exhibit activity towards various resistant strains of M. tuberculosis. Extensive applications of alkaloids in the field of therapeutics is well-established and nowday's researches being pursued to develop new potent drugs from natural sources for tuberculosis. Alkaloids are categorized in quite a few groups according to their structures and isolation from both terrestrial and marine sources. These new drugs might be a watershed in the battle against tuberculosis. This review summarizes alkaloids, which were found active against Mycobacteria since last ten years with special attention on the study of structure-activity relationship (SAR) and mode of action with their impact in drug discovery and development against tuberculosis.

A new antifungal eudesmanolide glycoside isolated from Sphaeranthus indicus Linn. (Family Compositae).

A new antifungal eudesmanolide glycoside 11,13-dihydro-3-O-(ß-digitoxopyranose)-7α-hydroxy eudasman-6,12-olide (2) in addition to known compounds 1 and 3, has been isolated from Sphaeranthus indicus Linn. Its structure was determined by spectral analysis (UV, IR, 1D and 2D NMR and mass spectrum).

Extract from Ceratonia siliqua Exhibits Depigmentation Properties.

Skin hyper-pigmentation is a condition initiated by the overproduction of melanin existing in the melanocytes. Melanin pigment is responsible for the colour of skin in humans. It is formed through a series of oxidative reactions involving the amino acid tyrosine in the presence of the key enzyme tyrosinase. In continuation with our efforts to identify tyrosinase inhibitors from plants sources, the methanol extract from leaf, bark and fruit of Ceratonia siliqua were screened for tyrosinase inhibition and diphenolase activity. The bark extract exhibited significant inhibition on mushroom tyrosinase using L-tyrosine as a substrate and showed diphenolase activity. The extract further significantly lowered tyrosinase mRNA levels in B16-F10 mouse melanocytes. Bioassay-guided fractionation led to the isolation of six compounds. Compounds (-)-epicatechin-3-O-gallate, 1,2,3,6-tetra-O-galloyl-ß-D-glucose and gallocatechin-3-O-gallate showed tyrosinase inhibitions with the IC50 values of 27.52, 83.30 and 28.30 µg/mL, respectively. These compounds also exhibited L-DOPA activities with IC50 values of >200, 150 and 200 µg/mL, respectively. A clinical study was conducted using 20 volunteers in a patch testing trial for irritancy potential and skin depigmentation. The clinical results showed the sample to be non-irritant with irritancy potential of -34.21 and depigmentation trial showed an improvement in the even skin tone of UV induced pigmentation at 3% after 28 days of application.

Cytotoxicity of syringin and 4-methoxycinnamyl alcohol isolated from Foeniculum vulgare on selected human cell lines.

This study was carried out to determine the cytotoxic effect of seven plant extracts and the isolated compounds - syringin and 4-methoxycinnamyl alcohol - on cancerous and non-cancerous cells. The ethanol extract of Foeniculum vulgare was found to exhibit the most significant toxicity with an IC50 value of 19.97 µg/mL on HeLa cells. Bioassay-guided fractionation led to the isolation of two compounds, syringin (1) and 4-methoxycinnamyl alcohol (2). Both compounds showed toxicity against MCF-7, HeLa and DU145 cancer cell line. The results showed that compound 2 showed high toxicity against all the cancer cell lines with IC50 values of 14.24, 7.82 and 22.10 µg/mL, respectively. 4-Methoxycinnamyl alcohol also showed no apoptotic effect in cell cycle analysis after 48 h at a concentration of 10 µg/mL. However, DNA fragmentation study revealed that necrosis took place at a concentration of 10 µg/mL after 48 h exposure.

Cytotoxicity of synthesized 1,4-naphthoquinone analogues on selected human cancer cell lines.

In an effort to establish new candidates with enhanced anticancer activity of 5-hydroxy-7-methyl-1,4-naphthoquinone scaffold (7-methyljuglone) previously isolated from the root extract of Euclea natalensis, a series of 7-methyljuglone derivatives have been synthesized and assessed for cytotoxicity on selected human cancer lines. These compounds were screened in vitro for anticancer activity on MCF-7, HeLa, SNO and DU145 human cancer cell lines by MTT assay. Most of them exhibited significant toxicity on cancer cell lines with lower IC50 values. The most potent derivative (19) exhibited the toxicity on HeLa and DU145 cell lines with IC50 value of 5.3 and 6.8µM followed by compound (5) with IC50 value of 10.1 and 9.3µM, respectively. Structure-activity relationship reveals that the fluoro substituents at position C-8 while hydroxyl substituents at C-2 and C-5 positions played an important role in toxicity.

Are plants used for skin care in South Africa fully explored?

ETHNOPHARMACOLOGICAL RELEVANCE: South Africa is an important focal point of botanical diversity, and although many plant species have been used since ancient times in ethnomedicine, only a few species have hitherto been fully investigated scientifically. A large proportion of the South African population use traditional medicines for their physical and psychological health needs. Many medicinal plants have recently gained popularity as ingredient in cosmetic formulations based on their ethnomedicinal values and many cosmetic products sold in stores are of natural origin. The present review discusses the ethnopharmacological values, pharmacological and toxicological evidence of 117 plant species grown in South Africa, which are used traditionally for skin care purposes. Special focus was on their traditional use for many skin disorders in order to identify their therapeutic potential, the state of ethnopharmacological knowledge and special emphasis has been on areas which require further research. MATERIALS AND METHODS: The information regarding all 117 plant species mentioned was extracted from Sci-Finder, Science direct, Medline and Google Scholar. All the available relevant data for medicinal plants was collated from literature review articles from the 19th century to early 2013. RESULTS: The extracts from different parts of plants exhibited significant pharmacological properties, proving significant skin care potentials. Special emphasis was on those plant species which still need further exploration and these have been documented separately. CONCLUSIONS: Despite the immense use of plants in ethnomedicine for skin care, limited research has been done on the activity of the crude extracts and very little on the active constituents. Consequently, almost 35 out of the 117 species are totally unexplored in the area of skin care. This investigation would be of interest to a broad readership including those researchers working in this field. The plant species namely: Greyia flanaganii, Sideroxylon inerme, Sclerocarya birrea, Calodendrum capense, Hyaenanche globosa, Harpephyllum caffrum, Ximenia americana, Leucosidea sericea Artemisia afra, and six Aloe species have been scientifically validated by our research group for skin hyperpigmentation problems.

Antibacterial and anti-inflammatory effects of Syzygium jambos L. (Alston) and isolated compounds on acne vulgaris.

BACKGROUND: Acne vulgaris is a chronic skin disorder leading to inflammation as a result of the production of reactive oxygen species due to the active involvement of Propionibacterium acnes (P. acnes) in the infection site of the skin. The current study was designed to assess the potential of the leaf extract of Syzygium jambos L. (Alston) and its compounds for antibacterial and anti-inflammatory activity against the pathogenic P. acnes. METHODS: The broth dilution method was used to assess the antibacterial activity. The cytotoxicity investigation on mouse melanocyte (B16-F10) and human leukemic monocyte lymphoma (U937) cells was done using sodium 3'-[1-(phenyl amino-carbonyl)-3,4-tetrazolium]-bis-[4-methoxy-6-nitrobenzene sulfonic acid hydrate (XTT) reagent. The non-toxic concentrations of the samples was investigated for the suppression of cytokines interleukin 8 (IL 8) and tumour necrosis factor (TNF α) by testing the supernatants in the co-culture of the human U937 cells and heat killed P. acnes using enzyme immunoassay kits (ELISA). The statistical analysis was done using the Graph Pad Prism 4 program. RESULTS: Bioassay guided isolation of ethanol extract of the leaves of S. jambos led to the isolation of three known compounds namely; squalene, an anacardic acid analogue and ursolic acid which are reported for the first time from this plant. The ethanol extract of S. jambos and one of the isolated compound namely, anacardic acid analogue were able to inhibit the growth of P. acnes with a noteworthy minimum inhibitory concentration (MIC) value of 31.3 and 7.9 µg/ml, respectively. The ethanol extract and three commercially acquired compounds namely; myricetin, myricitrin, gallic acid exhibited significant antioxidant activity with fifty percent inhibitory concentration (IC50) ranging between 0.8-1.9 µg/ml which was comparable to that of vitamin C, the reference antioxidant agent. The plant extract, compounds ursolic acid and myricitrin (commercially acquired) significantly inhibited the release of inflammatory cytokines IL 8 and TNF α by suppressing them by 74 - 99%. TEM micrographs showed the lethal effects of selected samples against P. acnes. CONCLUSIONS: The interesting antibacterial, antioxidant and anti-inflammatory effects of S. jambos shown in the present study warrant its further investigation in clinical studies for a possible alternative anti-acne agent.

An antileishmanial prenyloxy-naphthoquinone from roots of Plumbago zeylanica.

Leishmania donovani, an obligate intracellular parasite of genus Leishmania causes visceral leishmaniasis that affects millions of people worldwide, especially in the Indian subcontinent and East Africa. Generic pentavalent antimonials have been the mainstay for therapy in the endemic regions due to efficacy and cost effectiveness but the growing incidence of their resistance has seriously hampered their use. This study discloses strong in vitro antileishmanial activity of 2-methyl-5 -(3'-methyl-but-2'-enyloxy)-[1,4]naphthoquinone (1), a prenyloxy-naphthoquinone isolated and characterised from roots of the plant Plumbago zeylanica (family-Plumbaginaceae). The observed EC50 for the compound 1 against promastigote and amastigote forms of L. donovani was significantly (p<0.001) lower than miltefosine, a reference drug. In context to limited treatment options and growing resistance for available drugs, compound 1 offers a greater prospect towards antileishmanial drug discovery and development.

A novel antifungal anthraquinone from seeds of Aegle marmelos Correa (family Rutaceae).

A new anthraquinone, 1-methyl-2-(3'-methyl-but-2'-enyloxy)-anthraquinone (1) has been isolated from seeds of Aegle marmelos Correa and was characterized on the basis of spectral analysis (UV, IR, 1H NMR, 13C NMR, 2D NMR and mass spectroscopy). The compound exhibited significant antifungal activity against pathogenic strains of Aspergillus species and Candida albicans in disc diffusion assay (MIC value of 6.25 microg/disc), microbroth dilution and percent spore germination inhibition assays (MIC value of 31.25-62.5 microg/ml).

Antifungal constituents isolated from the seeds of Aegle marmelos.

Antifungal constituents, 2-isopropenyl-4-methyl-1-oxa-cyclopenta[b]anthracene-5,10-dione and (+)-4-(2'-hydroxy-3'-methylbut-3'-enyloxy)-8H-[1,3]dioxolo[4,5-h]chromen-8-one in addition to known compounds imperatorin, beta-sitosterol, plumbagin, 1-methyl-2-(3'-methyl-but-2'-enyloxy)-anthraquinone, beta-sitosterol glucoside, stigmasterol, vanillin and salicin were isolated during phytochemical investigation on seeds of Aegle marmelos Correa.

Alkaloids as potential anti-tubercular agents.

An increasing incidence of deaths due to tuberculosis and the known drawbacks of the current existing drugs including the emergence of multi drug-resistant strains have led to a renewed interest in the discovery of new anti-tubercular agents with novel modes of actions. The recent researches focused on natural products have shown a useful way to obtain a potentially rich source of drug candidates, where alkaloids have been found more effective. The present review focuses on current epidemiology of tuberculosis, synergy of the disease with HIV, current therapy, available molecular targets and, highlights why natural products especially alkaloids are so important. The review summarizes alkaloids found active against mycobacteria from the mid-1980s to late 2008 with special attention on the study of structure-activity relationship (SAR).