Medicinal and mechanistic overview of artemisinin in the treatment of human diseases.

Artemisinin (ART) is a bioactive compound isolated from the plant Artemisia annua and has been traditionally used to treat conditions such as malaria, cancer, viral infections, bacterial infections, and some cardiovascular diseases, especially in Asia, North America, Europe and other parts of the world. This comprehensive review aims to update the biomedical potential of ART and its derivatives for treating human diseases highlighting its pharmacokinetic and pharmacological properties based on the results of experimental pharmacological studies in vitro and in vivo. Cellular and molecular mechanisms of action, tested doses and toxic effects of artemisinin were also described. The analysis of data based on an up-to-date literature search showed that ART and its derivatives display anticancer effects along with a wide range of pharmacological activities such as antibacterial, antiviral, antimalarial, antioxidant and cardioprotective effects. These compounds have great potential for discovering new drugs used as adjunctive therapies in cancer and various other diseases. Detailed translational and experimental studies are however needed to fully understand the pharmacological effects of these compounds.

Curative anti-typhoid effect of Detarium microcarpum Guill. & Perr. (Leguminosae) hydroethanolic extract root bark based-on in vivo and molecular docking analyses.

ETHNOPHARMACOLOGICAL RELEVANCE: Detarium microcarpum is used to treat typhoid fever, a major public health problem, by indigenous population in Africa. Though its preventive activities have been documented, the curative effect is still to be confirmed. AIM OF THE STUDY: This study aimed at evaluating the curative effects of the hydroethanolic extract of Detarium microcarpum root bark on Salmonella typhimurium-induced typhoid in rat and exploring the in-silico inhibition of some bacterial key enzymes. STUDY DESIGN: In vitro antioxydant, in vivo antisalmonella of the extract and in silico molecular docking assay on the isolated compounds were carried out to explore the anti-salmonella effects of Detarium microcarpum. MATERIAL AND METHODS: The in vitro antioxidant properties of the extract were evaluated using DPPH, ABTS and FRAP tests. The anti-salmonella activity of the extract was assessed through feacal sample from Salmonella typhimurium-infected rat cultured in Salmonella-Shigella agar (SS agar) medium. The affinity of isolated compounds (Rhinocerotinoic acid and Microcarposide) from the extract were performed on four key enzymes (Adenylosuccinate lyase, Acetyl coenzyme A synthetase, Thymidine phosphorylase and LuxS-Quorum sensor) using molecular docking simulation to elucidate the molecular level inhibition mechanism. RESULTS: Crude extract of D. microcarpum root bark showed variable activities on DPPH (RSa50: 6.09 ± 1.04 µg/mL), ABTS (RSa50: 24.46 ± 0.27), and FRAP (RSa50: 23.30 ± 0.23). The extract at all the doses exhibited significant healing effect of infected rats, with the complete clearance. The extract restored hematological, biochemical and histological parameters closed to the normal control. The molecular docking results indicates that rhinocerotinoic acid and microcarposide present more affinity to the LuxS-Quorum sensor and Acetyl coenzyme A synthetase protein as compared to the others. CONCLUSION: These results demonstrate potent anti-typhoid activities of the hydroethanolic of Detarium microcarpum root bark extract through antioxidant properties and high inhibitory affinity of its compounds on some bacterial key enzymes that justify its use as traditional medicine to typhoid fever.

Natural essential oils as a new therapeutic tool in colorectal cancer.

Colorectal cancer (CRC) is the third most revalent type of cancer in the world and the second most common cause of cancer death (about 1 million per year). Historically, natural compounds and their structural analogues have contributed to the development of new drugs useful in the treatment of various diseases, including cancer. Essential oils are natural odorous products made up of a complex mixture of low molecular weight compounds with recognized biological and pharmacological properties investigated also for the prevention and treatment of cancer. The aim of this paper is to highlight the possible role of essential oils in CRC, their composition and the preclinical studies involving them. It has been reviewed the preclinical pharmacological studies to determine the experimental models used and the anticancer potential mechanisms of action of natural essential oils in CRC. Searches were performed in the following databases PubMed/Medline, Web of science, TRIP database, Scopus, Google Scholar using appropriate MeSH terms. The results of analyzed studies showed that EOs exhibited a wide range of bioactive effects like cytotoxicity, antiproliferative, and antimetastatic effects on cancer cells through various mechanisms of action. This updated review provides a better quality of scientific evidence for the efficacy of EOs as chemotherapeutic/chemopreventive agents in CRC. Future translational clinical studies are needed to establish the effective dose in humans as well as the most suitable route of administration for maximum bioavailability and efficacy. Given the positive anticancer results obtained from preclinical pharmacological studies, EOs can be considered efficient complementary therapies in chemotherapy in CRC.

Preliminary Structure-Activity Relationship Study of the MMV Pathogen Box Compound MMV675968 (2,4-Diaminoquinazoline) Unveils Novel Inhibitors of Trypanosoma brucei brucei.

New drugs are urgently needed for the treatment of human African trypanosomiasis (HAT). In line with our quest for novel inhibitors of trypanosomes, a small library of analogs of the antitrypanosomal hit (MMV675968) available at MMV as solid materials was screened for antitrypanosomal activity. In silico exploration of two potent antitrypanosomal structural analogs (7-MMV1578647 and 10-MMV1578445) as inhibitors of dihydrofolate reductase (DHFR) was achieved, together with elucidation of other antitrypanosomal modes of action. In addition, they were assessed in vitro for tentative inhibition of DHFR in a crude trypanosome extract. Their ADMET properties were also predicted using dedicated software. Overall, the two diaminoquinazoline analogs displayed approximately 40-fold and 60-fold more potency and selectivity in vitro than the parent hit, respectively (MMV1578445 (10): IC50 = 0.045 µM, SI = 1737; MMV1578467 (7): IC50 = 0.06 µM; SI = 412). Analogs 7 and 10 were also strong binders of the DHFR enzyme in silico, in all their accessible protonation states, and interacted with key DHFR ligand recognition residues Val32, Asp54, and Ile160. They also exhibited significant activity against trypanosome protein isolate. MMV1578445 (10) portrayed fast and irreversible trypanosome growth arrest between 4-72 h at IC99. Analogs 7 and 10 induced in vitro ferric iron reduction and DNA fragmentation or apoptosis induction, respectively. The two potent analogs endowed with predicted suitable physicochemical and ADMET properties are good candidates for further deciphering their potential as starting points for new drug development for HAT.

An Updated Review on The Properties of Melissa officinalis L.: Not Exclusively Anti-anxiety.

Melissa officinalis L. is a plant of the Lamiaceae family known in numerous countries for its medicinal activities. This plant has been used since ancient times to treat different disorders, including gastrointestinal, cardiovascular, neurological, psychological conditions. M. officinalis contains several phytochemicals such as phenolic acids, flavonoids, terpenoids, and many others at the basis of its pharmacological activities. Indeed, the plant can have antioxidant, anti-inflammatory, antispasmodic, antimicrobial, neuroprotective, nephroprotective, antinociceptive effects. Given its consolidated use, M. officinalis has also been experimented with clinical settings, demonstrating interesting properties against different human diseases, such as anxiety, sleeping difficulties, palpitation, hypertension, depression, dementia, infantile colic, bruxism, metabolic problems, Alzheimer's disease, and sexual disorders. As for any natural compound, drug, or plant extract, also M. officinalis can have adverse effects, even though the reported events are very rare and the plant can be considered substantially safe. This review has been prepared with a specific research strategy, interrogating different databases with the keyword M. officinalis. Moreover, this work analyzes the properties of this plant updating currently available literature, with a special emphasis on human studies.

Implementation and continued validation of the malaria Plasmodium falciparum lactate dehydrogenase-based colorimetric assay for use in antiplasmodial drug screening.

Antimalarial drug discovery has been facilitated by the development of various in vitro drug susceptibility testing methods suitable for medium-throughput or high-throughput campaigns. Among many, the Plasmodium falciparum lactate dehydrogenase (PfLDH) assay has acceptable demand on equipment, labour, technical skills and affordability and offers a good opportunity for scientists in low- and middle-income countries to participate in the global effort of discovering future antimalarial drugs. Hence, to enable our search for novel antimalarial drugs, we implemented and examined assay conditions and validated the PfLDH-based method in our laboratory using a reference set of standard antimalarial drugs with known activity against Plasmodium falciparum strains. The PfLDH assay revealed acceptable linearity profiles of R2 = 0.97 and 0.92 for Pf3D7 and PfDd2, respectively, achieved at 2% parasitaemia and 1% haematocrit. The detection and quantitation limits (DL and QL) of the PfLDH-based assay were 0.09% and 0.4% parasitemia, respectively. The assay showed an acceptable average Z-factor between 0.76 and 0.79 and was considerably robust. The average interassay reproducibility via percent coefficient of variation (%CV) was 5.47 between independent experiments. Overall, the PfLDH-based method produced a reliable and reproducible drug screening profile for in vitro assays in our setting. There were no significant interassay variability or hazards of other screening assays.

Identification of 3,3'-O-dimethylellagic acid and apigenin as the main antiplasmodial constituents of Endodesmia calophylloides Benth and Hymenostegia afzelii (Oliver.) Harms.

BACKGROUND: Endodesmia calophylloides and Hymenostegia afzelii belong to the Guttiferae and Caesalpiniaceae plant families with known uses in African ethno-medicine to treat malaria and several other diseases. This study aimed at identifying antiplasmodial natural products from selected crude extracts from H. afzelii and E. calophylloides and to assess their cytotoxicity. METHODS: The extracts from H. afzelii and E. calophylloides were subjected to bioassay-guided fractionation to identify antiplasmodial compounds. The hydroethanol and methanol stem bark crude extracts, fractions and isolated compounds were assessed for antiplasmodial activity against the chloroquine-sensitive 3D7 and multi-drug resistant Dd2 strains of Plasmodium falciparum using the SYBR green I fluorescence-based microdilution assay. Cytotoxicity of active extracts, fractions and compounds was determined on African green monkey normal kidney Vero and murine macrophage Raw 264.7 cell lines using the Resazurin-based viability assay. RESULTS: The hydroethanolic extract of H. afzelii stem bark (HasbHE) and the methanolic extract of E. calophylloides stem bark (EcsbM) exhibited the highest potency against both Pf3D7 (EC50 values of 3.32 ± 0.15 µg/mL and 7.40 ± 0.19 µg/mL, respectively) and PfDd2 (EC50 of 3.08 ± 0.21 µg/mL and 7.48 ± 0.07 µg/mL, respectively) strains. Both extracts showed high selectivity toward Plasmodium parasites (SI > 13). The biological activity-guided fractionation led to the identification of five compounds (Compounds 1-5) from HasbHE and one compound (Compound 6) from EcsbM. Of these, Compound 1 corresponding to apigenin (EC50 Pf3D7, of 19.01 ± 0.72 µM and EC50 PfDd2 of 16.39 ± 0.52 µM), and Compound 6 corresponding to 3,3'-O-dimethylellagic acid (EC50 Pf3D7 of 4.27 ± 0.05 µM and EC50 PfDd2 of 1.36 ± 0.47 µM) displayed the highest antiplasmodial activities. Interestingly, both compounds exhibited negligible cytotoxicity against both Vero and Raw 264.7 cell lines with selectivity indices greater than 9. CONCLUSIONS: This study led to the identification of two potent antiplasmodial natural compounds, 3,3'-O-dimethylellagic acid and apigenin that could serve as starting points for further antimalarial drug discovery.

Curcumin nanoformulations for antimicrobial and wound healing purposes.

The development and spread of resistance to antimicrobial drugs is hampering the management of microbial infectious and wound healing processes. Curcumin is the most active and effective constituent of Curcuma longa L., also known as turmeric, and has a very long and strong history of medicinal value for human health and skincare. Curcumin has been proposed as strong antimicrobial potentialities and many attempts have been made to determine its ability to conjointly control bacterial growth and promote wound healing. However, low aqueous solubility, poor tissue absorption and short plasma half-life due its rapid metabolism needs to be solved for made curcumin formulations as suitable treatment for wound healing. New curcumin nanoformulations have been designed to solve the low bioavailability problem of curcumin. Thus, in the present review, the therapeutic applications of curcumin nanoformulations for antimicrobial and wound healing purposes is described.

Medicinal plants used in the treatment of tuberculosis - Ethnobotanical and ethnopharmacological approaches.

Tuberculosis is a highly infectious disease declared a global health emergency by the World Health Organization, with approximately one third of the world's population being latently infected with Mycobacterium tuberculosis. Tuberculosis treatment consists in an intensive phase and a continuation phase. Unfortunately, the appearance of multi drug-resistant tuberculosis, mainly due to low adherence to prescribed therapies or inefficient healthcare structures, requires at least 20 months of treatment with second-line, more toxic and less efficient drugs, i.e., capreomycin, kanamycin, amikacin and fluoroquinolones. Therefore, there exists an urgent need for discovery and development of new drugs to reduce the global burden of this disease, including the multi-drug-resistant tuberculosis. To this end, many plant species, as well as marine organisms and fungi have been and continue to be used in various traditional healing systems around the world to treat tuberculosis, thus representing a nearly unlimited source of active ingredients. Besides their antimycobacterial activity, natural products can be useful in adjuvant therapy to improve the efficacy of conventional antimycobacterial therapies, to decrease their adverse effects and to reverse mycobacterial multi-drug resistance due to the genetic plasticity and environmental adaptability of Mycobacterium. However, even if some natural products have still been investigated in preclinical and clinical studies, the validation of their efficacy and safety as antituberculosis agents is far from being reached, and, therefore, according to an evidence-based approach, more high-level randomized clinical trials are urgently needed.

Phytochemical and pharmacological properties of asperuloside, a systematic review.

Plants are a natural source of bioactive compounds such as secondary metabolites. These molecules, also called phytochemicals, are fundamental for plant survival and often show therapeutic properties used for the treatment of human diseases. Asperuloside is a secondary metabolite which belongs to iridoid glycosides and is commonly present in the plant family Rubiaceae. In this review we aim to summarize the scientific knowledge on asperuloside, with a special emphasis on its pharmacological properties as anti-viral, anti-malarial, anti-protozoal, anti-tumorigenic, anti-hypertensive, anti-obesity, immunomodulatory, anti-inflammatory and antioxidant agent. Preclinical studies in animal models suggest that asperuloside has therapeutic potential that could be evaluated in humans. However, despite its tangible phytochemical characteristics, no clinical trial has been performed so far. Thus, we hope that this review will facilitate scientific dissemination of asperuloside pharmacological properties and encourage researchers to evaluate both pharmacokinetic and toxicity of asperuloside in animal models. This will be the first step towards clinical studies in humans.

Plant natural products with anti-thyroid cancer activity.

Thyroid cancer is the most frequent endocrine malignancy, with more than 500,000 cases per year worldwide. Differentiated thyroid cancers are the most common forms with best prognosis, while poorly/undifferentiated ones are rare (2% of all thyroid cancer), aggressive, frequently metastasize and have a worse prognosis. For aggressive, metastatic and advanced thyroid cancer novel antitumor molecules are urgently needed and phytochemical products can be a rational and extensive source, since secondary plant metabolites can guarantee the necessary biochemical variability for therapeutic purpose. Among bioactive molecules that present biological activity on thyroid cancer, resveratrol, curcumin, isoflavones, glucosinolates are the most common and used in experimental model. Most of them have been studied both in vitro and in vivo on this cancer, but rarely in clinical trial. This review summarizes phytochemicals, phytotherapeutics and plant derived compounds used in thyroid cancer.

Malva species: Insights on its chemical composition towards pharmacological applications.

Malvaceae family is typical from the Mediterranean region, contains 240 genera and more than 4,200 species. They are most commonly used as ornamental plants, although they can also be conceived as a food resource and remedy for various diseases, such as digestive, respiratory, genitourinary, throat infections, and skeletal and skin disorders, as also injuries where they are profoundly applied for skin care and as antiseptic and demulcent. They also possess diuretic, lenitive, spasmolytic, and laxative effects, besides to be used as antidiarrheal. Thus, the present review provides in-depth data on Malva spp. potential applications and phytochemical composition for food and pharmaceutical industries. Habitat and cultivation conditions and the clinical reports related to its biological effects are also emphasized. Malva spp. possess a wide variety of chemical constituents (such as polysaccharides, coumarins, flavonoids, polyphenols, vitamins, terpenes, and tannins) found in different plant organs, especially in leaves and flowers, connected to their biological activity. In general, Malva spp. have rather moderate antimicrobial activity, high antiinflammatory and wound healing activities, strong antioxidant activity, and anticancer properties. Results from in vitro and in vivo experiments encourage more in-depth studies, namely clinical trials, towards to improve knowledge on the use of Malva spp. for the treatment of various health conditions in humans.

Convolvulus plant-A comprehensive review from phytochemical composition to pharmacy.

Convolvulus genus is a representative of the family of Convolvulaceae. Convolvulus plants are broadly distributed all over the world and has been used for many centuries as herbal medicine. Convolvulus genus contains various phytochemicals such as flavonoids, alkaloids, carbohydrates, phenolic compounds, mucilage, unsaturated sterols or terpenes, resin, tannins, lactones, and proteins. This review highlights the phytochemical composition, antimicrobial and antioxidant activities, application as food preservative, traditional medicine use, anticancer activities, and clinical effectiveness in human of Convolvulus plants. All the parts of Convolvulus plants possess therapeutic benefits; preliminary pharmacological data validated their use in traditional medicine. However, further preclinical and clinical experiments are warranted before any application in human health.

Phytochemicals in Prostate Cancer: From Bioactive Molecules to Upcoming Therapeutic Agents.

Prostate cancer is a heterogeneous disease, the second deadliest malignancy in men and the most commonly diagnosed cancer among men. Traditional plants have been applied to handle various diseases and to develop new drugs. Medicinal plants are potential sources of natural bioactive compounds that include alkaloids, phenolic compounds, terpenes, and steroids. Many of these naturally-occurring bioactive constituents possess promising chemopreventive properties. In this sense, the aim of the present review is to provide a detailed overview of the role of plant-derived phytochemicals in prostate cancers, including the contribution of plant extracts and its corresponding isolated compounds.

Melatonin in Medicinal and Food Plants: Occurrence, Bioavailability, and Health Potential for Humans.

Melatonin is a widespread molecule among living organisms involved in multiple biological, hormonal, and physiological processes at cellular, tissue, and organic levels. It is well-known for its ability to cross the blood-brain barrier, and renowned antioxidant effects, acting as a free radical scavenger, up-regulating antioxidant enzymes, reducing mitochondrial electron leakage, and interfering with proinflammatory signaling pathways. Detected in various medicinal and food plants, its concentration is widely variable. Plant generative organs (e.g., flowers, fruits), and especially seeds, have been proposed as having the highest melatonin concentrations, markedly higher than those found in vertebrate tissues. In addition, seeds are also rich in other substances (lipids, sugars, and proteins), constituting the energetic reserve for a potentially growing seedling and beneficial for the human diet. Thus, given that dietary melatonin is absorbed in the gastrointestinal tract and transported into the bloodstream, the ingestion of medicinal and plant foods by mammals as a source of melatonin may be conceived as a key step in serum melatonin modulation and, consequently, health promotion.

The Therapeutic Potential of Naringenin: A Review of Clinical Trials.

Naringenin is a flavonoid belonging to flavanones subclass. It is widely distributed in several Citrus fruits, bergamot, tomatoes and other fruits, being also found in its glycosides form (mainly naringin). Several biological activities have been ascribed to this phytochemical, among them antioxidant, antitumor, antiviral, antibacterial, anti-inflammatory, antiadipogenic and cardioprotective effects. Nonetheless, most of the data reported have been obtained from in vitro or in vivo studies. Although some clinical studies have also been performed, the main focus is on naringenin bioavailability and cardioprotective action. In addition, these studies were done in compromised patients (i.e., hypercholesterolemic and overweight), with a dosage ranging between 600 and 800 µM/day, whereas the effect on healthy volunteers is still debatable. In fact, naringenin ability to improve endothelial function has been well-established. Indeed, the currently available data are very promising, but further research on pharmacokinetic and pharmacodynamic aspects is encouraged to improve both available production and delivery methods and to achieve feasible naringenin-based clinical formulations.

Dioscorea Plants: A Genus Rich in Vital Nutra-pharmaceuticals-A Review.

Dioscorea species, known as "Yams," belong to family Dioscoreaceae. This genus consists of more than 600 species distributed from Africa, Asia, the Caribbean's South America, and the South Pacific islands. Their organoleptic properties make them the most widely used carbohydrate food and dietary supplements. The underground and/or aerial tubers represent valuable sources of proteins, fats, and vitamins for millions of people in West Africa. This review gives a shot of secondary metabolites of Dioscorea plants, including steroids, clerodane diterpenes, quinones, cyanidins, phenolics, diarylheptanoids, and nitrogen-containing compounds. This review collected the evidence on biological properties of description Dioscorea, including in-vitro and in-vivo studies. Dioscorea species contain promising bioactive molecules i.e. diosgenin that support their different biological properties, including antioxidant, hypoglycaemic, hypolipidemic, anti- antimicrobial, inflammatory, antiproliferative, androgenic, estrogenic, and contraceptive drugs. Indeed, besides its nutrient values, Dioscorea is a potential source of bioactive substances of interest in the prevention/treatment of several diseases, and thus represents a great challenge in developing countries. However, ethnomedicinal potential should be validated and further researches on pharmacological properties and phytochemical composition should be carried out. Particularly, doing some studies to convert the preclinical results to clinical efficacy should be guaranteed. Dioscorea, Food plant, Traditional use, Phytochemistry, Pharmacological activities.

Resveratrol: A Double-Edged Sword in Health Benefits.

Resveratrol (3,5,4'-trihydroxy-trans-stilbene) belongs to polyphenols' stilbenoids group, possessing two phenol rings linked to each other by an ethylene bridge. This natural polyphenol has been detected in more than 70 plant species, especially in grapes' skin and seeds, and was found in discrete amounts in red wines and various human foods. It is a phytoalexin that acts against pathogens, including bacteria and fungi. As a natural food ingredient, numerous studies have demonstrated that resveratrol possesses a very high antioxidant potential. Resveratrol also exhibit antitumor activity, and is considered a potential candidate for prevention and treatment of several types of cancer. Indeed, resveratrol anticancer properties have been confirmed by many in vitro and in vivo studies, which shows that resveratrol is able to inhibit all carcinogenesis stages (e.g., initiation, promotion and progression). Even more, other bioactive effects, namely as anti-inflammatory, anticarcinogenic, cardioprotective, vasorelaxant, phytoestrogenic and neuroprotective have also been reported. Nonetheless, resveratrol application is still being a major challenge for pharmaceutical industry, due to its poor solubility and bioavailability, as well as adverse effects. In this sense, this review summarized current data on resveratrol pharmacological effects.

Phytochemicals in Helicobacter pylori Infections: What Are We Doing Now?

In this critical review, plant sources used as effective antibacterial agents against Helicobacter pylori infections are carefully described. The main intrinsic bioactive molecules, responsible for the observed effects are also underlined and their corresponding modes of action specifically highlighted. In addition to traditional uses as herbal remedies, in vitro and in vivo studies focusing on plant extracts and isolated bioactive compounds with anti-H. pylori activity are also critically discussed. Lastly, special attention was also given to plant extracts with urease inhibitory effects, with emphasis on involved modes of action.