Endophytic fungi from medicinal plants: a treasure hunt for bioactive metabolites

Endophytic fungi are ubiquitous organisms found in the plants, residing intercellular or intracellular, at least for a portion of their lives without causing apparent symptoms of infection. Almost all plants are known to harbor endophytes. The choice of the plant to be used for exploring endophytes for bioactives is important. Therefore, medicinal plants which are known to be used since centuries as an alternative source of medicine, are a valuable source for bioprospecting endophytes. Nevertheless, due to many reasons there is a dire need for novel resources for novel drugs which can be an answer to many deadly diseases. It is in this context that the present review was envisaged. The review reveals the importance of endophytic fungi from medicinal plants as a source of bioactive and chemically novel compounds. The bioactive metabolites produced by endophytic fungi originate from different biosynthetic pathways and belong to diverse structural groups such as terpenoids, steroids, quinones, phenols, coumarins etc. Endophytes therefore, represent a chemical reservoir for new compounds such as, anticancer, immunomodulatory, antioxidant, antiparasitic, antiviral, antitubercular, insecticidal etc. for use in the pharmaceutical and agrochemical industries. Although, efforts have been made to accommodate as many examples as possible but the depth of the subject is so vast that it cannot be covered in one single review. This in itself speaks of the fact that endophytic fungi from medicinal plants is indeed a treasure worth searching. In the present review only some selected examples have been covered.     

Novel antioxidants isolated from plants of the genera Ferula, Inula, Prangos and Rheum collected in Uzbekistan

We examined the effects of 48 compounds isolated from Ferula pallida, F. penninervis, Inula macrophylla, Prangos pabularia, P. tschimganica and Rheum maximowiczii collected in Uzbekistan on ADP/Fe²⁺-induced lipid peroxidation of egg yolk phosphatidylcholine liposomes. Of those compounds, 23 inhibited ADP/Fe²⁺-induced lipid peroxidation and nine showed especially strong inhibition of lipid peroxidation. Most compounds that inhibited peroxidation scavenged the 1,1′-diphenyl-2-picrylhydrazyl (DPPH) radical, indicating that the inhibition was due to radical scavenging. However, some compounds did not scavenge DPPH but inhibited lipid peroxidation significantly, suggesting that their inhibitory effect was not due to radical scavenging but to some other mechanism, such as prevention of Fe²⁺ function. Thus, we found various new antioxidants, some of which had a unique mechanism of action, in Ferula, Inula, Prangos and Rheum plants collected in Uzbekistan as seeds used in medicine.     

Medicinal plants as potential male anti-infertility agents: a review

For millions of couples, the inability to have a child is a personal tragedy and a large proportion of childless people are confronted with social stigmatization (blame) and personal frustration. Formerly assigned to women, infertility of a couple is nowadays equitably distributed between the two sexes. Among the methods used to treat male infertility problems, medicinal plants have been used empirically as extracts, decoctions, fractions or semi-purified compounds. These herbal products are used in the treatment of a dysfunctioning of the libido, sexual asthenia, erection, and sperm disorders. Pharmacological activities of many of these plants have been shown in vitro using cells, in vivo (on laboratory animals) and human studies. For instance, extracts of Panax ginseng, Panax quinquefolius and Lepidium meyenii have shown positive effects on sexual desire; while extracts of Astragalus membranaceus, Asparagus racemous, Withania somnifera, Andrographis paniculata and Acanthopanax senticosus improved sperm parameters. Plants provide a treatment option that is affordable and available for infertile couples, and phytotherapy is an essential form of treatment in our health system. However, herbal products are still anarchically used in many regions and countries, and a great proportion of medicinal plants used traditionally to solve male reproductive disorders have not yet been scientifically evaluated. Therefore in this review, we have summarized most of the data dealing with the effects of plant extracts on mammalian reproductive functions.     

Medicinal plants as a fight against murine blood-stage malaria

ObjectiveMalaria is an infectious parasitic disease affecting most of countries worldwide. Due to antimalarial drug resistance, researchers are seeking to find another safe efficient source for treatment of malaria. Since many years ago, medicinal plants were widely used for the treatment of several diseases. In general, most application is done first on experimental animals then human. In this article, medicinal plants as antimalarial agents in experimental animals were reviewed from January 2000 until November 2020.Materials and methodsIn this systematic review published articles were reviewed using the electronic databases NCBI, ISI Web of knowledge, ScienceDirect and Saudi digital library to check articles and theses for M.Sc/Ph.D. The name of the medicinal plant with its taxon ID and family, the used Plasmodium species, plant part used and its extract type and the country of harvest were described.Results and conclusionThe reviewed plants belonged to 83 families. Medicinal plants of families Asteraceae, Meliaceae Fabaceae and Lamiaceae are the most abundant for use in laboratory animal antimalarial studies. According to region, published articles from 33 different countries were reviewed. Most of malaria published articles are from Africa especially Nigeria and Ethiopia. Leaves were the most common plant part used for the experimental malaria research. In many regions, research using medicinal plants to eliminate parasites and as a defensive tool is popular.     

Nigella sativa L.: Uses in traditional and contemporary medicines – An overview

There are several wild and cultivated plants that offer excellent opportunities for being used as herbal and therapeutic agents. The identification of medicinal properties of plants and their effectiveness in treating diseases are important components in medicinal plant research and this can pave ways for further improvements in traditional drug use. Climatic conditions and phytogeography in Pakistan are ideal for naturally occurring diverse flora and managed cultivation of hundreds of plants of medicinal significance. Nigella sativa commonly known as the black seed is an important medicinal plant that has been widely used as a multipurpose medicinal agent in different countries since old times. The plant is abundantly cultivated in Pakistan for uses as condiment and medicines. It possesses important classes of bioactive compounds among which thymoquinone has attracted significant attention from the scientific community because of its active role in treating a diverse spectrum of diseases. The black seeds are used for reducing adverse effects of arthritis, asthma, inflammation, liver and gastro disorders besides their potential role in diabetes and cancers. The focus of this review is to highlight the medicinal significance of N. sativa in traditional medicine and opportunities for exploitation in contemporary medicine.     

Endophytic fungi isolated from medicinal plants: future prospects of bioactive natural products from Tabebuia/Handroanthus endophytes

Medicinal plants are a rich source of natural products used to treat many diseases; therefore, they are the basis for a new drug discovery. Plants are capable of generating different bioactive secondary metabolites, but a large amount of botanical material is often necessary to obtain small amounts of the target substance. Nowadays, many medicinal plants are becoming rather scarce. For this reason, it is important to point out the interactions between endophytic microorganisms and the host plant, because endophytes are able to produce highly diverse compounds, including those from host plants that have important biological activities. Thence, this review aims at presenting the richness in bioactive compounds of the medicinal plants from Tabebuia and Handroanthus genera, as well as important aspects about endophyte-plant interactions, with emphasis on the production of bioactive compounds by endophytic fungi, which has been isolated from various medicinal plants for such a purpose. Furthermore, bio-prospection of natural products synthesized by endophytes isolated from the aforementioned genera used in traditional medicine could be used to treat illnesses.

     

A compilation of Bioactive Compounds from Ayurveda

This review deals with the key bioactive compounds and the role of medicinal plants in Ayurvedic systems of medicine in India and their earlier investigation. There has been an increase in demand for the Phytopharmaceutical products of Ayurvĕda in Western countries, because of the fact that the allopathic drugs have more side effects. Many pharmaceutical companies are now concentrating on manufacturing of Ayurvĕdic Phytopharmaceutical products. Ayurvĕda is the Indian traditional system of medicine, which also deals about pharmaceutical science. Different type of plant parts used for the Ayurvedic formulation; overall out line of those herbal scenario and its future prospects for the scientific evaluation of medicinal plants used by traditional healers are also discussed. In India most of them, where Ayurvedic treatment is frequently used, for their ailments and provides instructions to local people how to prepare medicine from the herbs. As much as possible importance is also given for the taxonomic literature.     

Plant protein-based hydrophobic fine and ultrafine carrier particles in drug delivery systems

For thousands of years, plants and their products have been used as the mainstay of medicinal therapy. In recent years, besides attempts to isolate the active ingredients of medicinal plants, other new applications of plant products, such as their use to prepare drug delivery vehicles, have been discovered. Nanobiotechnology is a branch of pharmacology that can provide new approaches for drug delivery by the preparation of biocompatible carrier nanoparticles (NPs). In this article, we review recent studies with four important plant proteins that have been used as carriers for targeted delivery of drugs and genes. Zein is a water-insoluble protein from maize; Gliadin is a 70% alcohol-soluble protein from wheat and corn; legumin is a casein-like protein from leguminous seeds such as peas; lectins are glycoproteins naturally occurring in many plants that recognize specific carbohydrate residues. NPs formed from these proteins show good biocompatibility, possess the ability to enhance solubility, and provide sustained release of drugs and reduce their toxicity and side effects. The effects of preparation methods on the size and loading capacity of these NPs are also described in this review.     

Bioactivities,bioactive compounds and chemical constituents of mangrove plants

This review article presents the traditional and medicinal uses, and examines recent investigations on the biological activities of extracts, and chemicals identified from mangroves and mangal associates. Metabolites identified from mangrove plants are classified according to ‘chemical classes’, and some of their structures are illustrated. The article also presents some of the functions of the chemicals present and attempt to emphasize and create an awareness of the great of potential mangroves and mangal associates possess as a source of novel agrochemicals, compounds of medicinal value, and a new source of many already known biologically active compounds. This revised version was published online in July 2006 with corrections to the Cover Date.     

Naturally occurring bioactive Cyclobutane-containing (CBC) alkaloids in fungi,fungal endophytes,and plants

This article focuses on the occurrence and biological activities of cyclobutane-containing (CBC) alkaloids obtained from fungi, fungal endophytes, and plants. Naturally occurring CBC alkaloids are of particular interest because many of these compounds display important biological activities and possess antitumour, antibacterial, antimicrobial, antifungal, and immunosuppressive properties. Therefore, these compounds are of great interest in the fields of medicine, pharmacology, medicinal chemistry, and the pharmaceutical industry. Fermentation and production of CBC alkaloids by fungi and/or fungal endophytes is also discussed. This review presents the structures and describes the activities of 98 CBC alkaloids.     

Investigation of some bioactive Thai medicinal plants

It has been estimated that plants are the most important source of medicine for more than 80% of the world’s population. Medicinal plants are a vital source of medication in developing countries. Despite the wealth of human experience and folklore concerning the medicinal uses of plants, proper scientific investigation has only been applied to a small fraction of the world’s plants. This is a cause of grave concern as plant species continue to disappear. A rapid response to this situation is urgently needed to prevent the disappearance of the plant species and the ethnopharmacological knowledge that accompanies them. In this review, recent work on the investigation of selected bioactive Thai medicinal plants is presented. Their biological activities against infectious diseases including antimalarial and anti-HIV, are highlighted, as well as their anticancer, antiulcer and anti-inflammatory properties. The chemical transformations of some selected compounds are discussed. This revised version was published online in June 2006 with corrections to the Cover Date.     

A review of medicinal plant of Middle East and North Africa (MENA) region as source in tuberculosis drug discovery

Tuberculosis (TB) is a disease that affects one-third of the world’s population. Although currently available TB drugs have many side effects, such as nausea, headache and gastrointestinal discomfort, no new anti-TB drugs have been produced in the past 30 years. Therefore, the discovery of a new anti-TB agent with minimal or no side effects is urgently needed. Many previous works have reported the effects of medicinal plants against Mycobacterium tuberculosis (MTB). However, none have focused on medicinal plants from the Middle Eastern and North African (MENA) region. This review highlights the effects of medicinal plants from the MENA region on TB. Medicinal plants from the MENA region have been successfully used as traditional medicine and first aid against TB related problems. A total of 184 plants species representing 73 families were studied. Amongst these species, 93 species contained more active compounds with strong anti-MTB activity (crude extracts and/or bioactive compounds with activities of 0–100 µg/ml). The extract of Inula helenium, Khaya senegalensis, Premna odorata and Rosmarinus officinalis presented the strongest anti-MTB activity. In addition, Boswellia papyrifera (Del) Hochst olibanum, Eucalyptus camaldulensis Dehnh leaves (river red gum), Nigella sativa (black cumin) seeds and genus Cymbopogon exhibited anti-TB activity. The most potent bioactive compounds included alantolactone, octyl acetate, 1,8-cineole, thymoquinone, piperitone, α- verbenol, citral b and α-pinene. These compounds affect the permeability of microbial plasma membranes, thus kill the mycobacterium spp. As a conclusion, plant species collected from the MENA region are potential sources of novel drugs against TB.     

金丝桃属植物研究进展

金丝桃属植物中许多种是传统草药．二总酮类、类黄酮类及间苯三酚类等次生代谢产物具有许多药理作用。因此近年来对该属植物的分泌结构、具药理作川的化学成分、快速繁殖以及分子水平的研究越来越多。本文就以上各方面的研究进展作一综述。     

Effects of leachate from understory medicinal plants on litter decomposition and soil enzyme activities of Betula albo-sinensis and Eucommia ulmoides

Aims Forest litter decomposition is an important factor affecting nutrient cycling and ecosystem stability. In a complex system with forest and understory medicinal plants, leachate from the medicinal plants enriched in plant secondary metabolites (PSM) may inhibit litter decomposition and soil enzyme activity of forest trees. Thus, inspection on whether or not this phenomenon exits is one important basis for selecting understory medicinal plants.Methods In this paper, typical forest species Betula albo-sinensis and Eucommia ulmoides and six species of common medicinal plants (Corydalis bungeana, Mentha haplocalyx, Houttuynia cordata, Nepeta cataria, Gynostemma pentaphyllum and Prunella vulgaris) in Qinling Mountains area were taken as objects, and the litter decomposition experiment was carried out. The leachate (water-extraction solution) from the stems and leaves of the medicinal materials were sprayed onto the litter in order to study the effects of leachate from understory plants on forests litter decomposition, nutrient release (carbon, nitrogen and phosphorus) and soil enzyme activity.Important findings For litter of B. albo-sinensis, the decomposition half-life and the turnover period were extended by 76% and 4.3 times, respectively, under H. cordata leachate treatment and the inhibitory effects on the release of carbon and nitrogen were also significant. While under G. pentaphyllum leachate treatment, the half-life of litter decomposition and turnover period were extended by 35% and 2.7 times, respectively, and the inhibitory effects on the release of carbon, nitrogen and phosphorus were all significant. The leachate from these two species of medicinal plants displayed significant inhibitory effects on seven kinds of soil enzymes (invertase, carboxymethyl cellulase, β-glucosidase, dehydrogenase, polyphenol oxidase, protease and phosphatase) activity. For litter of E. ulmoides, the decomposition half-life and the turnover period were extended by 1.7 times and 4.2 times respectively, under H. cordata leachate treatment; while they were extended by 1 times and 9 times respectively, under G. pentaphyllum leachate treatment. The leachate from these two species of medicinal plants displayed significant inhibitory effects on the release of carbon, nitrogen and phosphorus from litter decomposition and the activities of all seven kinds of soil enzymes. Therefore, results suggested that H. cordata and G. pentaphyllum should not be planted under B. albo-sinensis and E. ulmoides forests, or the interplanting density must be low to reduce the inhibitory effects of litter decomposition.     

Medicinal plants: active compounds,properties and antiproliferative effects in colorectal cancer

Cancer development consists of a multitude of steps that occur progressively starting with initial driver mutation(s), to tumorigenesis, and ultimately metastasis. However, relatively little is known about the key epigenetic events that lead to tumour progression and metastasis. On the other hand, it is widely known that cancer cells acquire instruments to circumvent programmed cell death. Epidemiological studies suggest that medicinal plants can act as epigenetic compounds promoting several strategies to override apoptosis, including the induction of programmed cell death, the arrest of cell proliferation, or both. Interestingly, around half of current pharmaceutical drugs have been derived, directly or indirectly, from natural sources. Many species have been recognized to have medicinal properties and beneficial impact on health, such as, antioxidant or anti-inflammatory activities, anti-mutagenic effects and anti-carcinogenic potential. This review thoroughly discusses about the chemical composition and biochemical properties of four medicinal and Mediterranean plants such as Aloe vera, Salvia officinalis L. (Sage), Rosmarinus officinalis L. (Rosemary) and Urtica dioica (Nettle), and compares the potential of these plants to modify proliferation, migration, angiogenesis and apoptosis in colorectal cancer.

     

Some novel approaches for radioprotection and the beneficial effect of natural products

Due to the increased use of ionizing radiation in various aspects of human life especially in areas pertaining to radiotherapy of cancer, food preservation, agriculture, industry and power generation, there is a need to develop an effective and non-toxic radioprotector. The currently available ones have many drawbacks including high cost, side effects and toxicity. Several novel approaches are on to locate a potent radioprotector. These include mimics of antioxidant enzymes, nitroxides, melatonin, growth factors, gene therapy, hyperthermia apart from natural products. The latter has several advantages since they are non-toxic with proven therapeutic benefits. These can be classified as natural compounds and plant extracts; polyherbal formulations; besides natural and semi-natural compounds of plant origin. A review of the above agents, their efficacy in radioprotection and possible mechanisms responsible has been carried out. As India and many Eastern countries have an enormous heritage of vast natural dietary and time tested medicinal resources it is worth exploring the possibility of developing efficient, economically viable and clinically acceptable radioprotectors for human application from these resources.     

Modification of miRNA Expression through plant extracts and compounds against breast cancer: Mechanism and translational significance

BackgroundCancer is hyper-proliferative, multi-factorial and multi-step, heterogeneous group of molecular disorders. It is the second most reported disease after heart diseases. Breast carcinoma is the foremost death causing disease in female population worldwide. Cancer can be controlled by regulating the gene expression. Current therapeutic options are associated with severe side effects and are expensive for the people living in under-developed countries. Plant derived substances have potential application against different diseases like cancer, inflammation and viral infections.HypothesisThe mechanism of action of the medicinal plants is largely unknown. Targeting gene network and miRNA using medicinal plants could help in improving the therapeutic options against cancer.MethodsThe literature from 135 articles was reviewed by using PubMed, google scholar, Science direct to find out the plants and plant-based compounds against breast cancer and also the studies reporting their mechanistic route of action both at coding and noncoding RNA levels.ResultsNatural products act as selective inhibitors of the cancerous cells by targeting oncogenes and tumor suppressor genes or altering miRNA expression. Natural compounds like EGCG from tea, Genistein from fava beans, curcumin from turmeric, DIM found in cruciferous, Resveratrol a polyphenol and Quercetin a flavonoid is found in various plants have been studied for their anticancer activity. The EGCG was found to inhibit proliferative activity by modulating miR-16 and miR-21. Similarly, DIM was found to down regulate miR-92a which results to modulate NFkB and stops cancer development. Another plant-based compound Glyceollins found to upregulate miR-181c and miR-181d having role in tumor suppression. It also found to regulate miR-22, 29b and c, miR-30d, 34a and 195. Quercetin having anti-cancer activity induce the apoptosis through regulating miR-16, 26b, 34a, let-7g, 125a and miR-605 and reduce the miRNA expression like miR-146a/b, 503 and 194 which are involved in metastasis.ConclusionTargeting miRNA expression using natural plant extracts can have a reverse effect on cell proliferation; turning on and off tumor-inducing and suppressing genes. It can be efficiently adopted as an adjuvant with the conventional form of therapies to increase their efficacy against cancer progression.     

Natural products for cancer chemotherapy

For over 40 years, natural products have served us well in combating cancer. The main sources of these successful compounds are microbes and plants from the terrestrial and marine environments. The microbes serve as a major source of natural products with anti‐tumour activity. A number of these products were first discovered as antibiotics. Another major contribution comes from plant alkaloids, taxoids and podophyllotoxins. A vast array of biological metabolites can be obtained from the marine world, which can be used for effective cancer treatment. The search for novel drugs is still a priority goal for cancer therapy, due to the rapid development of resistance to chemotherapeutic drugs. In addition, the high toxicity usually associated with some cancer chemotherapy drugs and their undesirable side‐effects increase the demand for novel anti‐tumour drugs active against untreatable tumours, with fewer side‐effects and/or with greater therapeutic efficiency. This review points out those technologies needed to produce the anti‐tumour compounds of the future.     

Recent developments on triazole nucleus in anticonvulsant compounds: a review

Epilepsy is one of the common diseases seriously threatening life and health of human. More than 50 million people are suffering from this condition and anticonvulsant agents are the main treatment. However, side effects and intolerance, and a lack of efficacy limit the application of the current anticonvulsant agents. The search for new anticonvulsant agents with higher efficacy and lower toxicity continues to be the focus and task in medicinal chemistry. Numbers of triazole derivatives as clinical drugs or candidates have been frequently employed for the treatment of various types of diseases, which have proved the importance of this heterocyclic nucleus in drug design and discovery. Recently many endeavours were made to involve the triazole into the anticonvulsants design, which have brought lots of active compounds. This work is an attempt to systematically review the research of triazole derivatives in the design and development of anticonvulsant agents during the past two decades.