Natural products and the development of selective antiprotozoal drugs

New drugs are urgently required for the treatment of amoebiasis, leishmaniasis, malaria and trypanosomiasis. In this review the potential of natural plant products as a source of antiprotozoal drugs is discussed with respect to biochemical differences between protozoa and hosts. Some of the ways in which pathogenic protozoa differ biochemically from their human hosts are described, and the modes of action of some antiprotozoal drugs which exploit these differences are mentioned. A selection of natural products of plant origin (alkaloids, terpenes, quinones and miscellaneous compounds) is illustrated with emphasis on their modes of action and potential for the development of selective antiprotozoal agents.     

Management of diabetic complications: A chemical constituents based approach

Ethnopharmacological relevance

Long term hyperglycemia leads to development of complications associated with diabetes. Diabetic complications are now a global health problem without effective therapeutic approach. Hyperglycemia and oxidative stress are important components for the development of diabetic complications. Over the past few decades, herbal medicines have attracted much attention as potential therapeutic agents in the prevention and treatment of diabetic complications due to their multiple targets and less toxic side effects. This review aims to assess the current available knowledge of medicinal herbs for attenuation and management of diabetic complications and their underlying mechanisms.

Material and methods

Bibliographic investigation was carried out by scrutinizing classical text books and peer reviewed papers, consulting worldwide accepted scientific databases (SCOPUS, PUBMED, SCIELO, NISCAIR, Google Scholar) to retrieve available published literature. The inclusion criteria for the selection of plants were based upon all medicinal herbs and their active compounds with attributed potentials in relieving diabetic complications. Moreover, plants which have potential effect in ameliorating oxidative stress in diabetic animals have been included.

Results

Overall, 238 articles were reviewed for plant literature and out of the reviewed literature, 127 articles were selected for the study. Various medicinal plants/plant extracts containing flavonoids, alkaloids, phenolic compounds, terpenoids, saponins and phytosterol type chemical constituents were found to be effective in the management of diabetic complications. This effect might be attributed to amelioration of persistent hyperglycemia, oxidative stress and modulation of various metabolic pathways involved in the pathogenesis of diabetic complications.

Conclusion

Screening chemical candidate from herbal medicine might be a promising approach for new drug discovery to treat the diabetic complications. There is still a dire need to explore the mechanism of action of various plant extracts and their toxicity profile and to determine their role in therapy of diabetic complications. Moreover, a perfect rodent model which completely mimics human diabetic complications should be developed.     

Phenolic‐Linked Biochemical Rationale for the Anti‐Diabetic Properties of Swertia chirayita (Roxb. ex Flem.) Karst.

The crude extract of Swertia chirayita, an important medicinal plant of Nepal, is locally used for many diseases including type 2 diabetes. In this study, crude aqueous and 12% ethanol solution extracts of S. chirayita collected from nine districts of Nepal were analyzed for anti‐diabetic‐linked anti‐hyperglycemia potential using in vitro biochemical assays. There was moderate‐to‐high positive correlation between antioxidant activity and total phenolic content of both extracts and moderate‐to‐high α‐glucosidase inhibitory activity. Although the anti‐diabetic property of S. chirayita is mainly attributed to the phytochemical swerchirin present in its hexane fraction, we propose that the crude extract of this plant used in local healing also has anti‐hyperglycemia potential. The crude extracts indicated the presence of three main phytochemicals mainly mangiferin, swertiamarin, and amarogentin and their derivatives. Among the standard compounds (mangiferin, swertiamarin, and amarogentin), mangiferin showed α‐glucosidase and 2,2‐diphenyl‐1‐picrylhydrazyl radical inhibitory activity indicating anti‐hyperglycemia potential. Copyright © 2012 John Wiley & Sons, Ltd.     

Can ethnopharmacology contribute to the development of antiviral drugs?

In recent years, many compounds having potent antiviral activity in cell cultures and in experimental animals have been detected, but only a few have been approved by Western health authorities for clinical use. Nevertheless, some of these compounds are currently undergoing either preclinical or clinical evaluation, and perspectives for finding new interesting antiviral drugs are promising. Among these antiviral substances are several natural compounds isolated from plants used in traditional medicine including polysaccharides, flavonoids, terpenes, alkaloids, phenolics and amino acids. Some of these plant compounds exhibit a unique antiviral mechanism of action and are good candidates for further clinical research. What follows is a brief summary of the selection methods of plants for antiviral screening and in vitro and in vivo assays, which are currently used for detecting this activity in plant extracts. The importance of the plant kingdom as a source of new antiviral substances will be illustrated by presenting a survey on plant-derived antirhinovirus and anti-HIV agents.     

In Vitro and In Vivo Inhibitory Activities of Four Indian Medicinal Plant Extracts and their Major Components on Rat Aldose Reductase and Generation of Advanced Glycation Endproducts

The polyol enzyme aldose reductase (AR) and advanced glycation endproducts (AGEs) play an important role in diabetic complications such as cataracts. The purpose of this study was to investigate four standardized plant extracts used for the treatment of diabetes and related diseases, and their principal components for AR inhibitory activity and to find out their influence in diabetic complications. Thus, Boswellia serrata Triana & Planch. (Burseraceae), Lagerstroemia speciosa (L.) Pers. (Lythraceae), Ocimum gratissimum (L.) (Lamiaceae) and Syzygium cumin (L.) Skeels. (Myrthaceae) and their respective major constituents, boswellic acid, corosolic acid, ursolic acid and ellagic acid, were studied for their inhibitory activity against rat lens AR, rat kidney AR, human recombinant AR and generation of AGEs. In addition, in vivo inhibition of lens galactitol accumulation by the major constituents of the plants in galactose‐fed rat has been studied. The results revealed that all the tested extracts and their active ingredients possess significant AR inhibitory actions in both in vitro and in vivo assays with urosolic acid showing the most potent effect. Furthermore, the study indicates the potential of the studied plants and their major constituents as possible protective agents against long‐term diabetic complications. Copyright © 2012 John Wiley & Sons, Ltd.     

Reporter gene assays and their applications to bioassays of natural products

Medicinal plants represent precious resources from which bioactive compounds can be isolated and developed into invaluable therapeutic agents. With the advent of modern drug discovery technologies such as combinatorial chemistry and high-throughput drug screening platforms, there is an increasing interest in utilizing medicinal plants as a source of drug leads. A wide spectrum of bioassays can be employed for the detection of bioactivity in extracts, fractions, as well as purified compounds of herbal origin. Amongst the different types of bioassays, reporter gene assays are highly versatile and reliable. The present review provides an overview of the most popular reporter genes in terms of their basic methodology, capacities and limitations. The different types of intracellular and extracellular reporter gene products and their potential applications in bioassays of natural products are also discussed.     

Recent advances and future directions in anti‐tumor activity of cryptotanshinone: A mechanistic review

In respect to the enhanced incidence rate of cancer worldwide, studies have focused on cancer therapy using novel strategies. Chemotherapy is a common strategy in cancer therapy, but its adverse effects and chemoresistance have limited its efficacy. So, attempts have been directed towards minimally invasive cancer therapy using plant derived‐natural compounds. Cryptotanshinone (CT) is a component of salvia miltiorrihiza Bunge, well‐known as Danshen and has a variety of therapeutic and biological activities such as antioxidant, anti‐inflammatory, anti‐diabetic and neuroprotective. Recently, studies have focused on anti‐tumor activity of CT against different cancers. Notably, this herbal compound is efficient in cancer therapy by targeting various molecular signaling pathways. In the present review, we mechanistically describe the anti‐tumor activity of CT with an emphasis on molecular signaling pathways. Then, we evaluate the potential of CT in cancer immunotherapy and enhancing the efficacy of chemotherapy by sensitizing cancer cells into anti‐tumor activity of chemotherapeutic agents, and elevating accumulation of anti‐tumor drugs in cancer cells. Finally, we mention strategies to enhance the anti‐tumor activity of CT, for instance, using nanoparticles to provide targeted drug delivery.     

Murraya paniculata (L.) (Orange Jasmine): Potential Nutraceuticals with Ameliorative Effect in Alloxan‐Induced Diabetic Rats

Orange jasmine, Murraya paniculata (Rutaceae), is a plant from India widely used in folk medicine as antinociceptive, antiinflammatory, and antioxidant. Although oral hypoglycemic agents and insulin are the mainstays of treatment of diabetes mellitus (DM), there is a significant demand for new natural products to reduce the development of diabetic complications. Alloxan‐induced diabetic rats were treated for 60 days with a hydroalcoholic extract of M. paniculata (MPE), at doses of 100, 200, and 400 mg/kg. MPE decreased glycemia and also cholesterol and triglyceride levels, starting 1 week after treatments, as compared with the same group before treatments. Glucose values were reduced toward normality after 1 week of treatment. MPE hypoglycemic effects were potentiated by glibenclamide and metformin. MPE also decreased fructosamine and glycated hemoglobin values. MPE reduced diabetes‐induced morphological alterations of the kidney, pancreas, and liver. MPE acts similarly to glibenclamide and metformin, and its glucose‐lowering action is partly a consequence of ATP‐sensitive K⁺ channel inhibition. MPE may be a potential therapeutic alternative for the treatment of diabetes and its complications. Copyright © 2017 John Wiley & Sons, Ltd.     

Medicinal plants and antimicrobial activity

In the present paper, we analyze the past, present and future of medicinal plants, both as potential antimicrobial crude drugs as well as a source for natural compounds that act as new anti-infection agents. In the past few decades, the search for new anti-infection agents has occupied many research groups in the field of ethnopharmacology. When we reviewed the number of articles published on the antimicrobial activity of medicinal plants in PubMed during the period between 1966 and 1994, we found 115; however, in the following decade between 1995 and 2004, this number more than doubled to 307. In the studies themselves one finds a wide range of criteria. Many focus on determining the antimicrobial activity of plant extracts found in folk medicine, essential oils or isolated compounds such as alkaloids, flavonoids, sesquiterpene lactones, diterpenes, triterpenes or naphtoquinones, among others. Some of these compounds were isolated or obtained by bio-guided isolation after previously detecting antimicrobial activity on the part of the plant. A second block of studies focuses on the natural flora of a specific region or country; the third relevant group of papers is made up of specific studies of the activity of a plant or principle against a concrete pathological microorganism. Some general considerations must be established for the study of the antimicrobial activity of plant extracts, essential oils and the compounds isolated from them. Of utmost relevance is the definition of common parameters, such as plant material, techniques employed, growth medium and microorganisms tested.     

Medicinal bulbous plants of South Africa and their traditional relevance in the control of infectious diseases

Natural products are becoming more important in modern-day society as man is moving away from synthetic products, which can be detrimental to the environment and human health. Scientific research on the healing properties and bioactivity of natural compounds, especially of plant origin, has been extensive particularly in the Western world. However, a rich heritage of floral biodiversity is found in developing countries. South Africa, a country with a strong history of traditional healing, hosts a variety of around 30000 plant species. Indigenous bulbous plants of importance to South African traditional healers mainly belong to the Amaryllidaceae and Hyacinthaceae families. A number of these plants have particular uses as disinfectants and anti-inflammatory agents, although there is still a lack of scientific research regarding their unique pharmacological compounds.     

Molecular mechanisms of natural compounds in cell death induction and sensitization to chemotherapeutic drugs in lung cancer

Cancer remains one of the leading causes of death worldwide, especially lung cancer. Chemotherapeutic drugs are commonly used for lung cancer treatment; nonetheless, undesirable side effects and drug resistance remain major challenges for therapeutic success. Therefore, harmless and effective treatments against lung cancer are urgently required. The use of natural phytochemical products, in single or combinatorial therapy, is an emerging strategy for prevention and cure of cancer because of the various remarkable anticancer properties of these compounds. Cell death, which primarily occurs via apoptosis and nonapoptotic mechanisms (necrosis, autophagy, and cellular senescence), is one of the antineoplastic effects of natural compounds. In this review, we highlight representative plant‐derived compounds with cancer chemopreventive and sensitizing effects in combination with chemotherapeutic drugs with various cell death‐inducing mechanisms. Relevant molecular mechanisms implicated in the pharmacological effects of these natural compounds are discussed. Overall, this review provides a reference and new perspective for application of phytochemical agents as potential anti‐lung cancer drugs for further cancer drug research and development.     

Phytochemical and Pharmacological Profile of Vitex negundo

The article aims to review all the chemical constituents and pharmacological properties of Vitex negundo L. (Verbenaceae) (VN). VN is an important medicinal plant used as reputed herbal medicine with versatile pharmacological activities in China, India and Japan. A total of 104 referred articles about VN were compiled from major databases and academic publishers, such as MEDLINE, Pubmed, Scholar, Elsevier, Springer, Wiley and CNKI. As a result, a total of 120 compounds isolated from VN can be divided mainly into four classes: flavonoids, lignans, terpenoids and steroids. The crude extracts and purified compounds of VN exhibited promising bioactivities, including anti‐nociceptive, antiinflammatory, anti‐tumor, anti‐oxidant, insecticidal, antimicrobial, anti‐androgenic, anti‐osteoporotic, anti‐cataract, hepatoprotective and anti‐hyperglycemic activity. All the reported data lead us to conclude that VN has convincing medicinal potential. However, further researches are needed to explore its bioactive constituents, the structure–activity relationship and their molecular mechanisms of action. Copyright © 2015 John Wiley & Sons, Ltd.     

A modern look at folkloric use of anti-infective agents

Infectious diseases are of ancient origin, and mankind has a venerable history of use of higher plant extracts for the therapy of such infections. Some such agents survive in use from earlier times--quinine, emetine, and sanguinarine, for example--but the modern use of fermentation-based antibiotics has greatly overshadowed work on agents from other sources. After a brief review of the present status of the field of antibiotics, this review focuses upon the present status of antimicrobial agents from higher plants with particular reference to agents from plants with a folkloric reputation for treatment of infections. In particular, recent work on the tropical genus Erythrina is emphasized. The use of modern microbiological techniques demonstrates that higher plants frequently exhibit significant potency against human bacterial and fungal pathogens, that many genera are involved, that many folkloric uses can be rationalized on this basis, that the active constituents are readily isolated by bioassay-directed techniques, that their chemical structures are types uncommon amongst fermentation-based agents but are familiar to natural product chemists, that their antimicrobial spectra are comparatively narrow but that their potency is often reasonable, that they are comparatively easy to synthesize and the unnatural analogues so produced can possess enhanced therapeutic potential and, thus, it is concluded that such work generates a gratifying number of novel lead structures and that the possibility of finding additional agents for human or agricultural use based upon higher plant agents is realistic.     

Natural medicines used in the traditional Chinese medical system for therapy of diabetes mellitus

The rapidly increasing diabetes mellitus is becoming a serious threat to mankind health in all parts of the world. The control and treatment of diabetes and its complications mainly depend on the chemical or biochemical agents, but the fact is that it has never been reported that someone had recovered totally from diabetes. With the distinctive traditional medical opinions and natural medicines mainly originated in herbs, the traditional Chinese medicine performed a good clinical practice and is showing a bright future in the therapy of diabetes mellitus and its complications. Based on a large number of chemical and pharmacological research work, numerous bioactive compounds have been found in Chinese medicinal plants for diabetes. The present paper reviews 86 natural medicines with regards to their origin, anti-diabetic active principles and/or pharmacological test results, which are commonly used in the traditional Chinese medical system and have demonstrated experimental or/and clinical anti-diabetic effectiveness. Among these natural medicines, 82 originate from plants and 4 from animals or insects, which covers 45 families. It is strongly significant to pay close attention to traditional Chinese medical therapeutics and natural medicines for treatment of diabetes mellitus and its complications.     

Supplementation with Herbal Extracts to Promote Behavioral and Neuroprotective Effects in Experimental Models of Parkinson's Disease: A Systematic Review

Parkinson's disease (PD) consists of a neurodegenerative pathology that has received a considerable amount of attention because of its clinical manifestations. The most common treatment consists of administering the drugs levodopa and biperiden, which reduce the effectiveness of the disease and the progress of its symptoms. However, phytotherapy treatment of PD has shown great potential in retarding the loss of dopaminergic neurons and minimizing the behavioral abnormalities. The aim of this study is to systematically review the use of supplemental herbal plants with cellular protective effect and behavioral activity in in vivo and in vitro experimental models. A total of 20 studies were summarized, where the effectiveness of herbal extracts and their isolated bioactive compounds was observed in animal models for PD. The main neurochemical mechanisms found in these studies are schematically represented. The herbal extracts and their biocompounds have antioxidant, anti‐apoptotic, and antiinflammatory properties, which contribute to avoiding neuronal loss. Reports show that besides acting on the biosynthesis of dopamine and its metabolites, these compounds prevent D2 receptors' hypersensitivity. It is suggested that further studies need be conducted to better understand the mechanisms of action of the bioactive compounds distributed in these plants. Copyright © 2017 John Wiley & Sons, Ltd.     

Inhibition of Th1 and Th17 Cells by Medicinal Plants and Their Derivatives: A Systematic Review

Searching for new natural drugs that are capable of targeting Th1 and Th17 may lead to development of more effective treatments for inflammatory and autoimmune diseases. Most of the natural drugs can be derived from plants that are used in traditional medicine and folk medicine. The aim of this systematic review is to identify and introduce plants or plant derivatives that are effective on inflammatory diseases by inhibiting Th1 and Th17 responses. To achieve this purpose, the search terms herb, herbal medicine, herbal drug, medicinal plant, phytochemical, traditional Chinese medicine, Ayurvedic medicine, natural compound, inflammation, inflammatory diseases, Th1, Th17, T helper 1 or T helper 17 were used separately in Title/Keywords/Abstract in Web of Science and PubMed databases. In articles investigating the effect of the medicinal plants and their derivatives in inhibiting Th1 and Th17 cells, the effects of eight extracts of the medicinal plants, 21 plant‐based compounds and some of their derivatives, and eight drugs derived from the medicinal plants' compounds in inhibiting Th1 and Th17 cells were reviewed. The results showed that medicinal plants and their derivates are able to suppress Th17 and Th1 T cell functions as well as cytokine secretion and differentiation. The results can be used to produce herbal drugs that suppress Th, especially Th17, responses. Copyright © 2017 John Wiley & Sons, Ltd.     

Pharmacological and chemical features of Nepeta L. genus: Its importance as a therapeutic agent

Medicinal plants have always had great value for the human population due to their valuable constituents and potential bioactivities. The objective of this review is to present an updated overview of an important medicinal plant genus Nepeta L., from the family Lamiaceae, revealing its traditional utilization, biological activity, phytoconstituents, and mechanisms of action. For this purpose, a literature survey was carried out by using SciFinder, ScienceDirect, Scopus, PubMed, and Web of Science followed by a revision of the bibliographies of the related articles. We have described and analyzed the role of plants in drug discovery and the importance of Nepeta species. Information on the utilization purposes of Nepeta species in folk medicine has been emphasized, and scientific studies on the biological effects and secondary metabolites are addressed. Nepeta species are characterized by terpenoid‐type compounds and phenolic constituents, which exert several activities such as an antimicrobial, repellent against major pathogen vector mosquitoes, insecticide, larvicide against Anopheles stephensi, cytotoxic anticarcinogen, antioxidant, anticonvulsant, analgesic, anti‐inflammatory agent, and antidepressant, revealing its importance in medicinal and agricultural fields. On the basis of numerous studies, the Nepeta genus demonstrates remarkable therapeutic effects against various diseases. However, clinical studies are warranted to confirm preclinical findings.     

Biological effects of red beetroot and betalains: A review

Over the past few years, the use of natural substances as protective or therapeutic agents has gained much attention worldwide. Recent modern studies have shown a variety of health benefits for red beetroot and its active compounds betalains (also betanin) such as antioxidative, anti‐inflammation, anticancer, blood pressure and lipid lowering, also antidiabetic and anti‐obesity effects. Betanin, the main component of the red beetroot, is a betalain glycosidic pigment, which is used as a food additive. This review summarizes findings in the literature and shows the therapeutic potential of red beetroot and its active compounds (betalains) as promising alternatives for supplemental therapies in multiple diseases.     

Investigation in rats of the antihyperglycemic effect of plant extracts used in taiwan for the treatment of diabetes mellitus

In order to clarify the hypoglycemic activity of plants that are widely used to treat diabetes mellitus in Taiwan, the present study investigated the effectiveness of ten plant extracts by screening the decrease of blood glucose level in streptozocin-induced diabetic rats. We found that only six plant extracts exhibited blood glucose lowering activities in the rat. Blood levels of insulin were also determined using radioimmunoassay methods. Lack of an increase of insulin-like immunoreactivity in rats treated with these six plant extracts ruled out the mediation of insulin-dependent mechanisms. Similar effects were also observed in glucose-challenged rats treated with these extracts. The results confirmed the hypoglycemic activity of these plants and suggested that this action was produced through an insulin-independent mechanism.     

In vitro antiprotozoan activity and mechanisms of action of selected Ghanaian medicinal plants against Trypanosoma,Leishmania, and Plasmodium parasites

Trypanosomiasis, leishmaniasis, and malaria are protozoan infections of public health importance with thousands of new cases recorded annually. Control of these infection(s) with existing chemotherapy is limited by drug toxicity, lengthy parenteral treatment, affordability, and/or the emergence of resistant strains. Medicinal plants on the other hand are used in the treatment of various infectious diseases although their chemical properties are not fully evaluated. In this study, we screened 112 crude extracts from 72 selected Ghanaian medicinal plants for anti‐Trypanosoma, anti‐Leishmania, and anti‐Plasmodium activities in vitro and investigated their mechanisms of action. Twenty‐three extracts from 20 plants showed significant antiprotozoan activity against at least 1 of 3 protozoan parasites screened with IC₅₀ values less than 20 μg/ml. Eleven extracts showed high anti‐Trypanosoma activity with Bidens pilosa whole plant and Morinda lucida leaf extracts recording the highest activities. Their IC₅₀ (selectivity index [SI]) values were 5.51 μg/ml (35.00) and 5.96 μg/ml (13.09), respectively. Nine extracts had high anti‐Leishmania activity with Annona senegalensis and Cassia alata leaf extracts as the most active. Their IC₅₀ (SI) values were 10.8 μg/ml (1.50) and 10.1 μg/ml (0.37), respectively. Six extracts had high anti‐Plasmodium activity with the leaf and stem‐bark extracts of Terminalia ivorensis recording the highest activity. Their IC₅₀ (SI) values were 7.26 μg/ml (129.36) and 17.45 μg/ml (17.17), respectively. Only M. lucida at 25 μg/ml induced significant apoptosis‐like cell death in Trypanosoma parasites. Anti‐Leishmania active extracts induced varying morphological changes in Leishmania parasites such as multiple nuclei and/or kinetoplast, incomplete flagella division, or nuclear fragmentation. Active extracts may be potential sources for developing new chemotherapy against these infections.