Natural Products Journal, The - Volume 11, Issue 2, 2021

Diabetes remains the major public health challenge to the 21st century. It is strongly related to lifestyle changes. Most chronic complications of diabetes are macrovascular and microvascular diseases resulting from the existing hyperglycemic status. After the failure of first-line therapy, which is based on diet modifications and exercise, conventional treatment using antihyperglycemic agents with different mechanisms of action will be implemented for type II diabetes in modern medicine. Higher Basidiomycetes mushrooms are highly praised for their nutritional value and pharmacological properties. They have long been used traditionally for the maintenance of health, prevention and treatment of various human ailments. Reports indicate the beneficial effects of medicinal mushrooms in diabetes treatments. However, scientific evidence are insufficient to make definitive conclusions on the efficacy of individual medicinal mushrooms. Mushrooms belong to the genera Phellinus such as Phellinus linteus, Phellinus ribis, Phellinus rimosus and Phellinus igniarius. They possess a significant hypoglycemic effect in experimental diabetic models. However, well-designed controlled clinical trials are needed to establish their safety and bioactivity.

Tecoma stans (L.) Juss. ex Kunth has shown potent antidiabetic effect in the past; however, none of the studies have been carried out to explore its effect in diabetic complications including diabetic retinopathy and nephropathy. Thus, this review will aim to explore and propose multiple hypotheses regarding its mechanism of action in diabetic complications which includes reduction in oxidative stress, inflammation, angiogenesis, lipid profile correction and direct anti-glycemic effects. A detailed review including most of the articles, which includes research as well as reviews, available on the internet regarding the concerned topic was performed. The review includes MEDLINE databases using keywords along with their combinations, such as diabetic complications, plants in diabetes, Tecoma stans, renin oxidative stress, inflammation, angiogenesis, diabetic retinopathy, α- glucosidase and α-amylase, among several others. Mostly English-language articles were selected. Since it has already been reported in various studies that Tecoma stans exhibit anti-diabetic effect, however no information regarding its effects in diabetic complications were reported. This review presents the data which aids in confirming that Tecoma stans can provide promising results in oxidative stress, inflammation, angiogenesis and lipid peroxidation. Furthermore, it has been depicted that Tecoma stans has the potential for α-glucosidase inhibition. The mechanism below can explain that Tecoma stans can be used in diabetic complications of diabetic nephropathy and retinopathy. Tecoma stans may provide an effective natural product to treat hyperglycaemia and prevent subsequent diabetic complications which includes nephropathy and retinopathy.

Bamboo species belonging to the Poaceae family, Poaceae has overall about 1,500 species, and 87 genera worldwide, randomly distributed between humid tropical, sub-tropical and mildmoderate regions across the globe. The plant has superior value in traditional indigenous systems of China, Ayurveda, Siddha, and Unani for its enormous medicinal and nutritional purposes since 2500 years. It was the apparent beginning of bamboo used as a medication, which was trailed by a series of modern research and consequently formed a core scientific ingredient in a research laboratory. The current review is a critical study for the evaluation of state-of-the-art concerning phytochemistry, pharmacology and traditional uses of bamboo species of different genera, which put forward systemic research stratagems and to streamline the therapeutic exploration for the management of human ailments. The present review documents systemic overview of the scientific reports relating to the different bamboo species from older text, ancient literature available in the last five to six decades, e-books and various online databases (PubMed, MEDLINE, Scopus, Google Scholar, Springer, Francis , SciFinder, etc.). Additional information was acquired from conference proceedings, botanical books, and dissertations for this work. Bamboo species belonging to six different genera were explored for its medicinal and ethnomedicinal uses for treatment of inflammatory disorders, ulcers, diabetes, solid tumour, blood purifier, menstrual disorders, and infertility to name a few. The therapeutic potentials, along with their mechanism of action, are concisely deliberated and recapitulated in this review. Bamboo is rich in its nutritive value and has been explored as food and fodder. Studies related to the biological activity of bamboo species revealed that they possess twenty-one promising activities such as anticancer, antidiabetic, cardioprotective, anti-inflammatory, antioxidant, hepatoprotective, neuroprotective, and antibacterial. Eighty-two phytochemical studies have been summarized in this review which is majorly due to the presence of secondary active metabolites such as phenolics, flavonoids, terpenoids, steroid glycosides and coumarins along with minor constituents like polysaccharides, ketones, tannins, lignans, vitamins, amino acids, minerals, and essential oils. A critical assessment of the compiled scientific literature indicates serious efforts for systemic evaluation of the traditional claims and to identify, isolate and evaluate the phytoconstituents for nutritional and therapeutic potentials. Although the plant has immense potential in the health care system, still there is abundant need and avenues for commercialisation and awareness to society for the use of new health care products of bamboo. The present review affirms that bamboo owing to its rich phytochemical spectrum is the epitome plant with a vast potential for the pharmaceutical, cosmeceutical, nutraceutical, and food industry.

Deguelin, a plant retinoid has emerged to be a promising therapeutic agent in the treatment of different cancers. Recent studies demonstrate that deguelin has potential as an angiogenesis antagonist in malignant and endothelial cells by specifically targeting HGF-c-Met and VEGFVEGFR pathways. It is reported to have profound therapeutic effects in pancreatic cancer by inactivation of the hedgehog (Hh) signalling pathway and suppresses the expression of matrix metalloproteinases such as MMP-2 and MMP-9. The basic underlying mechanisms for deguelin mediated anti- NSCLC effects were uncovered through its induction of elevated intracellular Reactive Oxygen Species (ROS) levels and suppression of the PI3K /Akt-HK2 signalling pathway. Deguelin induces cell apoptosis by targeting various pathways most notably regulating the expression of galectin-1 and binding directly to anti-apoptotic Bcl-2 (B-cell lymphoma 2), Bcl-xl (B-cell lymphoma-extralarge) and Mcl-1 (Myeloid Cell Leukemia Sequence 1) in the hydrophobic grooves thereby liberating BAD and BAX from binding with these proteins. These results derived from the effect of Deguelin on various cancer cell lines have further elucidated its role as a novel anti-tumorigenic agent targeting angiogenesis, apoptosis, cell proliferation and migration for cancer chemoprevention. In this review, an attempt has been made to highlight the potential therapeutic effects of Deguelin in destroying the cancer cells by inhibiting various tumour promoting pathways and its uses as a therapeutic agent alone or in combination.

Background: Infectious diseases are responsible for millions of deaths a year worldwide. Antibiotics, which have saved so many lives and improved life expectancy, may become ineffective due to a worrying increase in bacterial resistance. Some of the appropriate actions that could be initiated to address this problem are to develop and search for new antimicrobial substances from medicinal plants, and combine antibiotics with antimicrobials agents isolated from a reservoir of bioactive natural products. Objectives: The purpose of this work was to study the chemical composition of the essential oil and hydrosol extract of Plumbago europaea, to evaluate their in-vitro antimicrobial activities and evaluate in-vitro combinatory antimicrobial effect of hydrosol extract with Gentamicin and Amphotericin B against a large panel of microorganisms in an effort to reduce their minimum effective dose and minimizing their side effects. Methods: The essential oil and hydrosol extract obtained from the roots of Plumbago europaea were analyzed by GC/MS and tested for their antibacterial and antifungal activities against twelve different strains of microorganisms. The effectiveness, in-vitro, of the association between the hydrosol extract and both Gentamicin and Amphotericin B was also investigated using the checkerboard method. Results: The obtained results revealed that nine and four components, representing for 92.4% and 97.4% of the total essential oil and hydrosol extract composition were identified, respectively and hydrosol extract was more active than the essential oil against all screened microorganisms, with interesting MIC values (19 μg/mL). An important effect of hydrosol extract was obtained in decreasing the MIC of Gentamicin and Amphotericin B in all tested combinations. Conclusion: The in-vitro combination of the hydrosol extract with Gentamicin and Amphotericin B led to substantial MIC reduction against all tested microorganisms. This combination can help to reduce the minimum effective dose of antimicrobial drugs used, which may help to decrease their side effects; and deliver these medicines with similar potency.

Background: Paederia foetida (Rubiaceae) locally known as Chinese fever vine is a prominent plant species in the east and south Asia. The extract of Paederia foetida Linn. has been used for the treatment of gastric infections or other digestive disorders in Chinese traditional medicine. Objective: The main aim of the study was to isolate bioactive constituents of P. foetida stem through a bio-guided assay, then evaluate their antibacterial activity and compare them with standard agents. Materials and Methods: The stems of P. foetida were extracted by methanol and successively partitioned with ethyl acetate and n-butanol. The ethyl acetate layer further fractionated using column chromatography and normal phase HPLC. The chemical structures of the isolated compounds were elucidated through comparison of the ¹H and ¹³C NMR and MS spectral data with the literature. The antibacterial activity of P. foetida stem was evaluated using agar well diffusion assay and resazurin based micro-dilution technique. Results: Ten compounds were isolated from the Chinese fever vine stem including four anthraquinones, morindaparvin A (1), 1,3-dihydroxy-2-methoxyanthraquinone (2), digiferrol (3), and alizarin (4); two steroids, β-sitosterol (5), and stigmastan-3-one (6); two coumarins, scopoletin (7) and fraxidin (8) and two aromatics, ferulic acid (9) and vanillic acid (10). The four anthraquinones 1-4 were isolated for the first time from Chinese fever vine stem. Compound 2 and 3 significantly inhibited Staphylococcus aureus with MIC values 18.75 and 9.37 μg/mL respectively, and streptomycin (1.8 μg/mL) was used as a positive control. Conclusion: Compound 2 and 3 can be considered as a prospective candidate for the treatment of staphylococcal bacterial infections in both human and animals.

Background: Aristolochia triangularis Cham., popularly known as the "cipó-milhomens", "angelicó" and "ypê-mi", is applied for the treatment of wounds, skin diseases (6,7), digestive and circulatory system diseases as an antipyretic and for malaria fever also. Objective: In this work, we investigated the chemical composition, the antimicrobial and antimycobacterial activities of the Essential Oils (EOs) extracted from A. triangularis fresh stems and leaves collected in Southern Brazil. Methods: Fresh stems and fresh leaves of Aristolochia triangularis Cham. were separately subjected to hydrodistillation using a Clevenger-type apparatus. The chemical composition of the Essential Oils (EOs) was analyzed by Gas Chromatography/Mass Spectrometry (GC/MS). The oil samples were evaluated for their antimycobacterial, antibacterial and antifungal activities against twenty-four microorganisms. Results: Hydrodistillation of fresh stems and leaves of A. triangularis resulted in 0.16% (w/w) and 0.37% (w/w) of light-yellow oils, respectively. Germacrene D was found in 13.2 - 13.5% in both the EOs. The constituent most abundant in the stems EO (19.18%) was the oxygenated diterpene ent- Kaur-16-en-19-al (10), along with E-nerolidol (17.89%). The main constituents of the leaves EO were bicyclogermacrene (24.79%), β-elemene (11.30%), E-caryophyllene (10.40%) and germacrene A (9.42%), in addition to the previously mentioned germacrene D. The stems and leaves EOs showed capacity to inhibit the Gram-negative Enterobacter aerogenes and the stems EO showed the capacity to inhibit Staphylococcus aureus, with MIC values of 31.2 μg/mL. S. aureus was found to be moderately sensitive to leaves EO, while stems EO displayed moderate activity against Enterococcus faecalis and Salmonella typhimurium (MIC values of 62.5 μg/mL). Candida glabrata was highly susceptible to both EOs (MIC values < 3.9 μg/mL). The EOs showed moderate potential to inhibit the growth of Cryptococcus gatti and Cryptococcus neoformans (MICs of 62.5 μg/mL). Conclusion: The A. triangularis essential oils from stems and leaves displayed the capacity to inhibit Enterobacter aerogenes (MIC values of 31.2 μg/mL) and high antifungal effect against Candida glabrata (MIC values of <3.9 μg/mL). Mycobacterium massiliense and M. abscessus were susceptible to the leaves EO, with MICs of 39.06 μg/mL. These results showed the potential of A. triangularis essential oils as antifungal and antimycobacterial agents to be used in the development of new antibiotics.

Background: Multi-drug resistance among pathogens is emerging due to the slow pace of development of new antimicrobials by combinatorial chemistry. Natural products from microorganisms obtained from under-explored habitats can be lead molecules for such discoveries. In search of new antimicrobial compounds, Streptomyces isolate UK-201 exhibiting broad-spectrum antimicrobial and antifungal activity, obtained from under-explored Lachhiwala Reserve forest, of the Himalayas was selected in this study. Objectives: The major objectives were to characterize isolate UK-201, taxonomically identify it based on 16S rDNA sequencing and execute metabolite fingerprinting of ethyl acetate extract of UK-201 by GC-MS. Methods: Isolate UK-201 was characterized by phenotypic, biochemical/physiological methods and identified by 16S rDNA sequencing. Ethyl acetate extract of this isolate exhibited antimicrobial activity against the selected panel of gram-positive, gram-negative bacteria and fungi. The extract was partially purified by column chromatography. Active fractions were pooled and analysed by GCMS. The obtained compounds were tentatively identified by collated data analysis based on Similarity Index, and observed and calculated Retention Indices. Results: Isolate UK-201 showed 97.46% similarity to Streptomyces niveiscabiei, 96.88% to S. sasae and S. puniciscabiei, 96.72% to S. capoamus and S. yaanensis. A low similarity percentage indicated the taxonomic novelty of the isolate and was confirmed by comparing it with phenotypic characteristics with the nearest matches. Metabolite fingerprinting showed the presence of twenty-four novel compounds. Conclusion: This study showed that bioprospection from under-explored habitats conferred novel bio and chemodiversity.

Aims: To isolate vinca alkaloid producing endophytic fungi from Catharanthus roseus and the evaluation of the factors which enhance the vincristine production. Background: An endophytic fungus Botryosphaeria laricina (CRS1) isolated from Catharanthus roseus demonstrated vinca alkaloid production under certain conditions. Objective: To Understand the conditions under which the fungus was able to produce vincristine and vinblastine. Methods: Fungal isolates from C. roseus were grown in liquid culture and screened for alkaloid production. The strain (CRS1) producing catharanthine was sequenced and matched with GenBank. This isolated strain was studied for production of vinca alkaloids and the conditions required for vincristine and vinblastine production. Results: Eight endophytic fungi were isolated from the fresh aerial parts of C. roseus. Only CRS1, demonstrated catharanthine production. DNA sequencing of CRS1 gave a 100% match with the GenBank accession number, KC509580.1, which is related to the Botryosphaeria laricina strain JAS6. CRS1 produced only catharanthine when cultured in Czapek’s peptone liquid medium (CZ). Addition of C. roseus fresh plant extract (8.0 mL) to the culture medium (4.0 L) stimulated the production of catharanthine (3.2 mg), catharanthinic acid (0.3 mg), N-demethyl-vinblastine (0.3 mg), vinblastine (2.8 mg) and vincristine (2.4 mg). However, if the added plant extract was preheated (80 °C, for 15 min), no vinca alkaloids appeared other than catharanthine. To identify the active fractions of the plant extract stimulating vinca alkaloid production, the extract was dialyzed in buffer at 4 °C through 20 kDa MW cutoff membrane to separate into two fractions of molecules above and below 20 kDa MW. Only the fraction containing molecules above 20 kDa was able to transform catharanthine to vincristine and vinblastine. When the dialysis was performed in water instead of buffer, the larger fraction could only produce catharanthine and vinblastine. Other conditions such as the presence of light:dark (12:12 h), fructose (30.0 g L^-1), glucose (30.0 g L^-1), Cu²⁺ (0.1 mM) ions, L-tryptophan (0.1%) and succinic acid (1%) did not induce alkaloid production. Conclusion: The catharanthine producing fungal strain B. laricina (CRS1) could only produce the two vinca alkaloids, vinblastine and vincristine from catharanthine in the presence of active components larger than 20 kDa MW present in the plant extract of C. roseus.

Background: One of the four most incident plant species in mangrove is the Laguncularia racemosa, widely used in popular medicine against inflammation and fever. Objective: Here, L. racemosa was investigated in relation to their phytochemical profile, antioxidant activity, cytotoxicity, antimicrobial and immunostimulatory effect. Methods: Aqueous extract was obtained from leaves of plant, its phytochemical profile was investigated through UPLC method, the antioxidant assays performed were TAA, DPPH, ABTS, nitrite and lipid peroxidation assay. Antimicrobial assays were made using standard strains. For all biological tests were used mice splenocytes and from these cell cultures were measured cytotoxicity, proliferation index and cytokines production. Results: Laguncularia racemosa leaves showed the presence of ions, proteins, carbohydrates, vitamins and high concentration of phenolic compounds. Antioxidant activities were promoted by aqueous extract, especially in DPPH and NO assays. Extract in 6 μg/mL did not induce significant cell death, stimulated the cell proliferation and the IL-4 production. Moreover, decreases of proinflammatory cytokines IFN-γ, TNF-α and IL-6 were found. Conclusion: The presence of essential nutrients, significant antioxidant activity and immune stimulation confirm the use of this plant in folk medicine against inflammation.

Background: Sarasvata churna is an Ayurvedic formulation for treatment and management of epilepsy and other maniac disorders since thousands of years. Objective: This study aimed to evaluate the in vitro antioxidant potential, total phenolics and flavonoids content, acute-oral-toxicity and anticonvulsant activity of Sarasvata churna. Materials & Methods: In vitro antioxidant activity of methanolic extract of Sarasvata churna against Nitrous oxide, Peroxide, Phosphomolybdenum and Hydroxyl radicals was performed using Colorimetry against Ascorbic acid as standard along with estimation of total phenolic and flavonoids content. Acute oral toxicity was evaluated using OECD guidelines. Extract in carboxymethyl cellulose at doses of 50,75,100,125,150 and 200 mg/kg was screened for anticonvulsant activity using subcutaneous Pentylenetetrazole and Maximal Electroshock models in Swiss Albino Mice (n=6). Sodium valproate was used as standard. Results: IC50 value of methanolic extract in the Nitrous oxide, Peroxide, and Hydroxyl free radical scavenging assay was found to be 165mg/ml, 32.5mg/ml and 253.9mg/ml respectively as compared to 61.58μg/ml, 333.44μg/ml and 351μg/ml respectively of standard Ascorbic acid. In acute oral toxicity screening, animals did not show any signs of acute and delayed toxicity even up to a dose of 2000mg/kg. Extract offered a protection of 57.39% and 85.26% in scPTZ model (P<0.0001) and 74% and 96.38% in MES model (P<0.0001) at doses of 50 and 200mg/kg respectively as compared to standard at 95% Confidence interval (ANNOVA, Tukey test) indicating a dose-dependent protection. Conclusion: Sarasvata churna’s potentials are comparable with standard antioxidant Ascorbic acid and antiepileptic drug Sodium valproate. This preclinical and toxicity screening data can be beneficial in establishing the scientific basis for the use of Sarasvata churna in management of epilepsy.