Propolis: An update on its chemistry and pharmacological applications.

Propolis, a resinous substance produced by honeybees from various plant sources, has been used for thousands of years in traditional medicine for several purposes all over the world. The precise composition of propolis varies according to plant source, seasons harvesting, geography, type of bee flora, climate changes, and honeybee species at the site of collection. This apiary product has broad clinical applications such as antioxidant, anti-inflammatory, antimicrobial, anticancer, analgesic, antidepressant, and anxiolytic as well asimmunomodulatory effects. It is also well known from traditional uses in treating purulent disorders, improving the wound healing, and alleviating many of the related discomforts. Even if its use was already widespread since ancient times, after the First and Second World War, it has grown even more as well as the studies to identify its chemical and pharmacological features, allowing to discriminate the qualities of propolis in terms of the chemical profile and relative biological activity based on the geographic place of origin. Recently, several in vitro and in vivo studies have been carried out and new insights into the pharmaceutical prospects of this bee product in the management of different disorders, have been highlighted. Specifically, the available literature confirms the efficacy of propolis and its bioactive compounds in the reduction of cancer progression, inhibition of bacterial and viral infections as well as mitigation of parasitic-related symptoms, paving the way to the use of propolis as an alternative approach to improve the human health. However, a more conscious use of propolis in terms of standardized extracts as well as new clinical studies are needed to substantiate these health claims.

Quantifying the Impact of Algae Supplement on Blood Pressure: Systematic Review and Meta-analysis of Randomized Controlled Trials.

The impact of Algae supplements and its extract on blood pressure has not concluded yet. The aim of this systematic review meta-analysis is to evaluate the antihypertensive activity of this group marine organism on human. Alga was used in some studies as capsules (from 500-mg to 8-g) and the follow-up duration changed from 17 days to 9 months. The difference in standardized mean and its corresponding 95% confidence interval (CI) was applied as the effect size of algae supplementation on systolic and diastolic blood pressure. Based on the results, a meta-analysis of 10 studies with baseline effect control demonstrated that there was no difference in the mean systolic blood pressure in the 2 groups SMD (95%CI): -1.05 (-2.85,0.76), but a significant difference in the mean diastolic blood pressure was observed and showed that the mean diastolic blood pressure in the treatment group was lower than the control group SMD(95%CI): -2.23 (-4.35,-0.11). A meta-analysis of 4 studies with no baseline control effect did not show significant results on both blood pressure. The evidence to support this systematic review meta-analysis requires more investigation and future large scale RCT clinical trial to confirm the results.

The effects of Ginsenosides on PI3K/AKT signaling pathway.

Ginsenosides belong to a group of steroid glycosides that are extracted from the plant genus Panax (ginseng). This plant has been used for a long time for the treatment of a variety of disorders in traditional medicine. Recent studies have assessed the biological impact of Ginsenosides in cell culture or animal models. Animal studies have shown their beneficial impacts in the remedy of pathological conditions in different tissues. The ameliorating effects of Ginsenosides in diverse pathogenic conditions can be attributed to their effects on the production of reactive oxygen species. These substances mainly affect the activity of AMPK/AKT and PI3K/AKT pathways. The beneficial effects of Ginsenosides have been appraised in diabetes-related complications, spinal cord injury, cerebral ischemia, myocardial ischemia, and other disorders which are associated with oxidative stress. Moreover, these substances have been shown to interfere with the pathologic conditions during carcinogenesis. In the current study, we explain these impacts in two distinct sections including non-neoplastic conditions and neoplastic conditions.

Nrf2-Related Therapeutic Effects of Curcumin in Different Disorders.

Curcumin is a natural polyphenol with antioxidant, antibacterial, anti-cancer, and anti-inflammation effects. This substance has been shown to affect the activity of Nrf2 signaling, a pathway that is activated in response to stress and decreases levels of reactive oxygen species and electrophilic substances. Nrf2-related effects of curcumin have been investigated in different contexts, including gastrointestinal disorders, ischemia-reperfusion injury, diabetes mellitus, nervous system diseases, renal diseases, pulmonary diseases, cardiovascular diseases as well as cancers. In the current review, we discuss the Nrf2-mediated therapeutic effects of curcumin in these conditions. The data reviewed in the current manuscript indicates curcumin as a potential activator of Nrf2 and a therapeutic substance for the protection of cells in several pathological conditions.

Improvement of Phenolic Compound Extraction by Using Ion Exchange Chromatography and Evaluation of Biological Activities of Polyphenol-enriched Fraction of Rosa canina Fruits.

Background: Rosa canina has been traditionally known as a medicinal plant. Different applications of fruits (Rose hip) comprise the food, perfume, and cosmetic industries. Objectives: This study aimed to prepare an enriched polyphenolic fraction from Rosa canina in addition to its biological activities. Methods: Poly phenolic enriched fraction was prepared using Amberlite XAD-7 for removing unwanted components. Phenols, flavonoids, and anthocyanins content analyses showed that they increased significantly compared to the extract. HPLC analysis showed that this fraction is a rich source of ascorbic acid. Results: The results of the DPPH, ferric-reducing antioxidant power (FRAP), ABTS, and nitric oxide assay confirmed that the antioxidant activities of the fraction had been increased compared to the extract. The oxygen radical absorbance capacity (ORAC) assay and cellular antioxidant activity of the fraction also confirmed its potential antioxidant activity. This fraction showed xanthine oxidase inhibitory activity at 100 µg/mL concentration. Comet assay analysis revealed that this fraction at 25 - 100 µg/mL concentrations inhibited H2O2 genotoxicity in human lymphocytes. Conclutions: This study suggests that the fruit of Rosa canina could be considered as a potential antioxidant, a xanthine oxidase inhibitor, and an antigenotoxic source, and the application of Amberlite XAD-7 improves extraction efficiencies through enrichment of phenolic compounds in this plant.

LC-ESI-QTOF-MS/MS characterization of phenolic compounds from Prosopis farcta (Banks & Sol.) J.F.Macbr. and their potential antioxidant activities.

Prosopis farcta (Banks & Sol.) J.F.Macbr. is an emerging medicinal plant containing a diverse array of phytochemicals, including protein, fat, carbohydrate, fibre, alkaloids, fatty acids, glycosides, and polyphenols, with strong antioxidant potential. However, the screening and characterization of phenolic compounds in P. farcta is limited. This study is conducted to determine the polyphenol contents and their antioxidant activity in P. farcta leaves samples via liquid chromatography-electrospray ionization quadrupole time-of-flight mass spectrometry (LC-ESI-QTOF-MS/MS) and high-performance liquid chromatography-photodiode array (HPLC-PDA). Total phenolic content (TPC), total flavonoid content (TFC), and total tannins content (TTC) were determined for polyphenol estimation. The antioxidant properties were measured by total antioxidant capacity (TAC), 2,2'-Diphenyl-2-picrylhydrazyl (DPPH), Ferric Reducing Antioxidant Power (FRAP), and 2,2"²-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS). LC-ESI-QTOF-MS/MS was used to identify and characterize 47 phenolic compounds, which mainly included phenolic acids (13), flavonoids (28), other polyphenols (4), lignans (1), and stilbenes (1). According to HPLC-PDA quantification, chlorogenic acid (9.78 ± 2.15 mg/g dw) was the most abundant phenolic acid, while the main flavonoids included catechin (12.73 ± 1.29 mg/g dw) and kaempferol (7.93 ± 1.47 mg/g dw). The study demonstrated the significance of P. farcta as a rich source of phenolic compounds with antioxidant capacity that can be widely used in food, beverage, feed, and pharmaceutical applications.

High-performance thin-layer chromatography fingerprinting and anti-inflammatory and antinociceptive activities of Pyracantha coccinea M.Roem.: A laboratory-based study.

This study aimed to investigate the high-performance thin-layer chromatography (HPTLC) fingerprinting and in-vivo anti-inflammatory and antinociceptive activities of different leaf extracts (ethanolic extract, n-hexane, chloroform, and ethyl acetate) of Pyracantha coccinea M.Roem. plant. A total of one hundred and twenty-four Wistar rats for anti-inflammatory and antinociceptive tests (carrageenan and formalin tests, respectively) were treated with two doses of the ethanolic extract (100 and 300 mg/kg), two doses of other plant fractions (30 and 100 mg/kg), Diclofenac (25 mg/kg) as the positive control, and normal saline as the negative control group, by oral gavage route. HPTLC fingerprinting is used for assay of terpenoids, flavonoids, alkaloids, and antioxidant activity. Treatment of the animal with the ethanolic extract at doses of 100 and 300 mg/kg, both ethyl acetate and chloroform fractions at the dose of 30 mg/kg and 100 mg/kg decreased the pain score in the formalin test and paw edema caused by carrageenan relative to control group significantly. Moreover, these extracts reported the highest amounts of flavonoid contents. In conclusion, phytochemicals present in Pyracantha coccinea M.Roem. leaves have anti-inflammatory and antinociceptive activities. Future studies are needed to identify the compounds with the anti-inflammatory and antinociceptive potential present in the plant.

Paclitaxel: Application in Modern Oncology and Nanomedicine-Based Cancer Therapy.

Paclitaxel is a broad-spectrum anticancer compound, which was derived mainly from a medicinal plant, in particular, from the bark of the yew tree Taxus brevifolia Nutt. It is a representative of a class of diterpene taxanes, which are nowadays used as the most common chemotherapeutic agent against many forms of cancer. It possesses scientifically proven anticancer activity against, e.g., ovarian, lung, and breast cancers. The application of this compound is difficult because of limited solubility, recrystalization upon dilution, and cosolvent-induced toxicity. In these cases, nanotechnology and nanoparticles provide certain advantages such as increased drug half-life, lowered toxicity, and specific and selective delivery over free drugs. Nanodrugs possess the capability to buildup in the tissue which might be linked to enhanced permeability and retention as well as enhanced antitumour influence possessing minimal toxicity in normal tissues. This article presents information about paclitaxel, its chemical structure, formulations, mechanism of action, and toxicity. Attention is drawn on nanotechnology, the usefulness of nanoparticles containing paclitaxel, its opportunities, and also future perspective. This review article is aimed at summarizing the current state of continuous pharmaceutical development and employment of nanotechnology in the enhancement of the pharmacokinetic and pharmacodynamic features of paclitaxel as a chemotherapeutic agent.

Diplazium esculentum (Retz.) Sw.: Ethnomedicinal, Phytochemical, and Pharmacological Overview of the Himalayan Ferns.

The genus Diplazium (family: Athyriaceae) comprises approximately 350 species of pteridophytes. Diplazium esculentum (Retz.) Sw. is an important member of this genus and commonly known as a wild vegetable in the Himalayan and sub-Himalayan communities. According to the literature analysis, D. esculentum was traditionally used for the prevention or treatment of several diseases such as diabetes, smallpox, asthma, diarrhea, rheumatism, dysentery, headache, fever, wounds, pain, measles, hypertension, constipation, oligospermia, bone fracture, and glandular swellings. Various extracts of D. esculentum were evaluated to elucidate their phytochemical and pharmacological activities. A wide array of pharmacological properties such as antioxidant, antimicrobial, antidiabetic, immunomodulatory, CNS stimulant, and antianaphylactic activities have been recognized in different parts of D. esculentum. The review covers a systematic examination of pharmacognosy, phytochemistry, and pharmacological applications of D. esculentum, but scientifically, it is not fully assessed regarding complete therapeutic effects, toxicity, and safety in the human body. The published literature on D. esculentum and its therapeutic properties were collected from different search engines including Wiley online, PubMed, Springer Link, Scopus, Science Direct, Web of Science, Google Scholar, and ACS publications by using specific terms such as "Diplazium esculentum, bioactive compounds, biological activities and health benefits" from 1984 to 2021 (March). Therefore, further studies are required to identify the detailed action mechanism of D. esculentum in vitro/in vivo, and also, more studies should focus on conservation, cultivation, and sustainable utilization of the species.

Phenolic Bioactives as Antiplatelet Aggregation Factors: The Pivotal Ingredients in Maintaining Cardiovascular Health.

Cardiovascular diseases (CVD) are one of the main causes of mortality in the world. The development of these diseases has a specific factor-alteration in blood platelet activation. It has been shown that phenolic compounds have antiplatelet aggregation abilities and a positive impact in the management of CVD, exerting prominent antioxidant, anti-inflammatory, antitumor, cardioprotective, antihyperglycemic, and antimicrobial effects. Thus, this review is intended to address the antiplatelet activity of phenolic compounds with special emphasis in preventing CVD, along with the mechanisms of action through which they are able to prevent and treat CVD. In vitro and in vivo studies have shown beneficial effects of phenolic compound-rich plant extracts and isolated compounds against CVD, despite that the scientific literature available on the antiplatelet aggregation ability of phenolic compounds in vivo is scarce. Thus, despite the current advances, further studies are needed to confirm the cardioprotective potential of phenolic compounds towards their use alone or in combination with conventional drugs for effective therapeutic interventions.

Naturally Occurring Bioactives as Antivirals: Emphasis on Coronavirus Infection.

The current coronavirus disease (COVID-19) outbreak is a significant threat to human health and the worldwide economy. Coronaviruses cause a variety of diseases, such as pneumonia-like upper respiratory tract illnesses, gastroenteritis, encephalitis, multiple organ failure involving lungs and kidneys which might cause death. Since the pandemic started there have been more than 107 million COVID-19 infections caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and ∼2.4 million deaths globally. SARS-CoV-2 is easily transmitted from person-to-person and has spread quickly across all continents. With the continued increase in morbidity and mortality caused by COVID-19, and the damage to the global economy, there is an urgent need for effective prevention and treatment strategies. The advent of safe and effective vaccines has been a significant step forward in the battle against COVID-19, however treatment of the symptoms associated with the disease still requires new anti-viral and anti-inflammatory drug therapies. To this end, scientists have been investigating available natural products that may be effective against SARS-CoV-2, with some products showing promise in fighting several viral infections. Since many natural products are dietary components or are prepared as dietary supplements people tend to consider them safer than synthetic drugs. For example, Traditional Chinese Medicines have been effectively utilized to treat SARS-CoV-2 infected patients with promising results. In this review, we summarize the current knowledge of COVID-19 therapies and the therapeutic potential of medicinal plant extracts and natural compounds for the treatment of several viral infections, with special emphasis on SARS-CoV-2 infection. Realistic strategies that can be employed for the effective use of bioactive compounds for anti-SARS-CoV-2 research are also provided.

The impact of the phytotherapeutic agent quercetin on expression of genes and activity of signaling pathways.

Quercetin is a flavonoid existing in different herbs, fruits, seeds, nuts and tea. It has beneficial effects on human health through mediating antioxidant activities, immune-modulatory impacts and regulating metabolic pathways. These effects are most probably induced through modulation of activity of signaling pathways and expression of genes. Several in vitro studies have verified anti-proliferative effects of quercetin and its effect on expression of apoptotic genes and cell cycle-related genes. Moreover, through modulation of a number of proteins such as NF-kB, PARP, STAT3, Bax, Bcl-2, COX2, and cytokines, quercetin has beneficial effects in neurodegenerative disorders, liver diseases and diabetes. PI3K/AKT is the mostly linked pathway with beneficial effects of quercetin. In the current manuscript, we explain the impact of quercetin on expression of genes and function of cellular signaling cascades in different contexts.

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.

High-performance thin-layer chromatography fingerprinting, total phenolic and total flavonoid contents and anti-platelet-aggregation activities of Prosopis farcta extracts.

Cardiovascular diseases are a leading cause of worldwide death and excessive platelet is closely related with their pathogenesis. Different plants and natural compounds have demonstrated anti-platelet effects. The aim of this study was to report the high-performance thin-layer chromatography (HPTLC) fingerprinting and anti-platelet-aggregation activities of different leaf extracts (n-hexane, chloroform, ethyl acetate, methanol and aqueous) of Prosopis farcta (Syrian mesquite) plant. The results showed a 100% inhibition of aggregation activity after plasmatic adenosine diphosphate (ADP) aggregation activation of ethyl acetate, ethanolic, methanolic and aqueous extracts, at 60 mg/mL concentration. The IC50 ADP value of these extracts ranged between 4.07 and 11.39 mg/mL. Moreover, these extracts reported the highest amounts of phenolic and flavonoid contents. In conclusion, phytochemicals present in P. farcta leaves have anti-platelet-aggregation activities. Future studies are needed to identify the compounds with anti-platelet potential present in P. farcta.

Phytochemical screening of Alstonia venenata leaf and bark extracts and their antimicrobial activities.

Alstonia venenata is a plant commonly found in South India and used in traditional medicine. The aim of this study was to characterize the phytochemicals present in A. venenata leaf and bark extracts and study their antimicrobial activities. Solvent extractions with Soxhlet apparatus of leaves and bark were obtained using hexane, benzene, isopropanol, methanol, and water. The crude extracts were concentrated and screened for qualitative phytochemical content and analyzed by thin layer chromatography. The antibacterial, antifungal and antiviral activities of crude extracts were measured by in vitro methods. Alkaloids, carbohydrates, tannins, phenolic compounds, terpenoids, cardiac glycosides and amino acids were found in the different crude extracts analyzed. Isopropanol extracts showed antifungal activity and it was more pronounced in the bark extract than the leaf extract. Moreover, the isopropanol extract exhibited antibacterial and antiviral activity. In conclusion, the leaves and bark of A. venenata have antimicrobial components which are more present in the isopropanol fraction.

Biological activities and health-promoting effects of Pyracantha genus: a key approach to the phytochemical's potential.

Pyracantha spp. are commonly called firethorn, and attract human attention due to their colorful berries. These berries are eaten globally as a traditional remedy for treating different stomach abnormalities, and as a cooking ingredient for folk diets. The present review aims to provide an overview on Pyracantha genus' geographical distribution and botanical description, traditional uses, phytochemical composition, biological activities and safety issues. Several biological activities have been reported to Pyracantha species, namely antioxidant, anti-inflammatory, antimicrobial, larvicidal and cytotoxic properties, most of them attributed to the use of their fruits. Pyracantha species phytochemical composition reveal the presence of interesting bioactive molecules, such as pyracrenic acid and fortuneanosides. The currently reported biological activities to these plants derive from in vitro and in vivo studies, so that clinical trials are needed to confirm these preclinical results. Nonetheless, Pyracantha species can be suggested as a safe herb useful to develop future drug formulations and functional foods.

Phytochemical screening of Alstonia scholaris leaf and bark extracts and their antimicrobial activities.

Alstonia sholaris is an evergreen tree commonly found in South East Asia. In traditional medicine pharmacological activities are attributed to the leaves and bark of this plant. The aim of this study is characterizing the chemicals present in A. sholaris leaves and bark extracts and study their antimicrobial activities. Solvent extractions with Soxhlet apparatus of leaves and bark were obtained using hexane, benzene, isopropanol, methanol, and water. The crude extracts were concentrated and screened for qualitative phytochemical analysis and thin layer chromatography, and the antibacterial, antifungal an antiviral activity of crude extracts were measured by in vitro methods. Isopropanol and methanol extracts showed significant antibacterial activity and it was more pronounced against Gram positive than against Gram negative bacteria. Hexane, benzene, isopropanol and methanol fractions of A. scholaris bark and leaf showed activity against Enterobacter cloacae. Isopropanol extract showed maximum activity against selected human pathogenic fungus. In conclusion, the leaves and bark of A. scholaris are rich in phytochemicals with antimicrobial activities against human pathogens, being the isopropanol fraction the one with the highest antibacterial, antifungal, antiviral and anti-mycobacterial activities.

Prosopis Plant Chemical Composition and Pharmacological Attributes: Targeting Clinical Studies from Preclinical Evidence.

Members of the Prosopis genus are native to America, Africa and Asia, and have long been used in traditional medicine. The Prosopis species most commonly used for medicinal purposes are P. africana, P. alba, P. cineraria, P. farcta, P. glandulosa, P. juliflora, P. nigra, P. ruscifolia and P. spicigera, which are highly effective in asthma, birth/postpartum pains, callouses, conjunctivitis, diabetes, diarrhea, expectorant, fever, flu, lactation, liver infection, malaria, otitis, pains, pediculosis, rheumatism, scabies, skin inflammations, spasm, stomach ache, bladder and pancreas stone removal. Flour, syrup, and beverages from Prosopis pods have also been potentially used for foods and food supplement formulation in many regions of the world. In addition, various in vitro and in vivo studies have revealed interesting antiplasmodial, antipyretic, anti-inflammatory, antimicrobial, anticancer, antidiabetic and wound healing effects. The phytochemical composition of Prosopis plants, namely their content of C-glycosyl flavones (such as schaftoside, isoschaftoside, vicenin II, vitexin and isovitexin) has been increasingly correlated with the observed biological effects. Thus, given the literature reports, Prosopis plants have positive impact on the human diet and general health. In this sense, the present review provides an in-depth overview of the literature data regarding Prosopis plants' chemical composition, pharmacological and food applications, covering from pre-clinical data to upcoming clinical studies.

Athyrium plants - Review on phytopharmacy properties.

Athyrium plants consist of more than 230 species that are largely distributed in the Sino-Himalayan region and the Western Pacific islands. Athyrium species are being used in traditional medicine worldwide to treat various ailments such as cough, rheumatic pain, scorpion stings, sores, burns and scalds, intestinal fever, pain, specifically breast pain during child birth, to increase milk flow, as an antiparasitic, anthelmintic, and carminative. A deep look in the literature has revealed that Athyrium species have been poorly investigated for their food preservative applications and in vivo and in vitro biological and phytochemical studies. However, some Athyrium species have demonstrated antimicrobial, anti-inflammatory, antioxidant, antiproliferative and anti-HIV potential. Athyrium multidentatum (Doll.) Ching is the most investigated species and the biological activities of their extracts, such as they antioxidant properties, seem to be related to the sulfate contents of their polysaccharides. This review provides an update on the ethnopharmacology, phytochemistry and biological properties of Athyrium plants that might be useful for further research. Of course, well-designed clinical trials will be required for some species to be used as therapy.

Triterpenoid corosolic acid attenuates HIF-1 stabilization upon cobalt (II) chloride-induced hypoxia in A549 human lung epithelial cancer cells.

Hypoxia-inducible factor-1 is a target for the management of cancer. Here, the anti-proliferation properties of corosolic acid (CA) against A549 human lung epithelial cancer cells in CoCl2-induced hypoxia is reported. CA was isolated from the roots of Salvia syriaca based on a bioassay-guided isolation platform and identified by 1D and 2D NMR experiments. Several cytotoxicies and genotoxicity analyses were performed using MTT, DAPI, cell cycle, DNA ladder, and annexin V/PI detection. Cobalt chloride (CoCl2) was used to stimulate hypoxia. The adaptation of A549 cells to a stimulated hypoxic condition in the presence of CA was evaluated. CA decreased the growth of A549 cells with an IC50 of 12 µg/mL at 48 h. Also, chromatin condensation and DNA fragmentation were detected as signs of apoptosis occurrence. CA induced ~85% apoptosis and even 1% necrosis. The expression of hypoxia-inducible factor-1 α (HIF-1α), HIF-1ß and downstream genes was strongly suppressed in the presence of CA in CoCl2-stimulated hypoxia condition. Results indicated that CA has remarkable cytotoxicity against the cancerous cell in hypoxia condition and may be regarded for preparation of new formulations for possible uses as supplement and medicine in cancer therapy.