Peptide Targeting of PDZ-Dependent Interactions as Pharmacological Intervention in Immune-Related Diseases

PDZ (postsynaptic density (PSD95), discs large (Dlg), and zonula occludens (ZO-1)-dependent interactions are widely distributed within different cell types and regulate a variety of cellular processes. To date, some of these interactions have been identified as targets of small molecules or peptides, mainly related to central nervous system disorders and cancer. Recently, the knowledge of PDZ proteins and their interactions has been extended to various cell types of the immune system, suggesting that their targeting by viral pathogens may constitute an immune evasion mechanism that favors viral replication and dissemination. Thus, the pharmacological modulation of these interactions, either with small molecules or peptides, could help in the control of some immune-related diseases. Deeper structural and functional knowledge of this kind of protein–protein interactions, especially in immune cells, will uncover novel pharmacological targets for a diversity of clinical conditions.     

Pharmacological Activities of Aminophenoxazinones

Aminophenoxazinones are degradation products resulting from the metabolism of different plant species, which comprise a family of natural products well known for their pharmacological activities. This review provides an overview of the pharmacological properties and applications proved by these compounds and their structural derivatives during 2000–2021. The bibliography was selected according to our purpose from the references obtained in a SciFinder database search for the Phx-3 structure (the base molecule of the aminophenoxazinones). Compounds Phx-1 and Phx-3 are among the most studied, especially as anticancer drugs for the treatment of gastric and colon cancer, glioblastoma and melanoma, among others types of relevant cancers. The main information available in the literature about their mechanisms is also described. Similarly, antibacterial, antifungal, antiviral and antiparasitic activities are presented, including species related directly or indirectly to significant diseases. Therefore, we present diverse compounds based on aminophenoxazinones with high potential as drugs, considering their levels of activity and few adverse effects.     

Phytochemicals from Polyalthia Species: Potential and Implication on Anti-Oxidant,Anti-Inflammatory,Anti-Cancer,and Chemoprevention Activities

Polyalthia belong to the Annonaceae family and are a type of evergreen tree distributed across many tropical and subtropical regions. Polyalthia species have been used long term as indigenous medicine to treat certain diseases, including fever, diabetes, infection, digestive disease, etc. Recent studies have demonstrated that not only crude extracts but also the isolated pure compounds exhibit various pharmacological activities, such as anti-oxidant, anti-microbial, anti-tumor, anti-cancer, etc. It is known that the initiation of cancer usually takes several years and is related to unhealthy lifestyle, as well as dietary and environmental factors, such as stress, toxins and smoking. In fact, natural or synthetic substances have been used as cancer chemoprevention to delay, impede, or even stop cancer growing. This review is an attempt to collect current available phytochemicals from Polyalthia species, which exhibit anti-cancer potentials for chemoprevention purposes, providing directions for further research on the interesting agents and possible clinical applications.     

Effects of ionizing radiation on bio-active plant extracts useful for preventing oxidative damages

Humans are exposed to ionizing radiations in medical radiodiagnosis and radiotherapy that cause oxidative damages and degenerative diseases. Airplane pilots, and even more astronauts, are exposed to a variety of potentially harmful factors, including cosmic radiations. Among the phytochemicals, phenols are particularly efficient in countering the oxidative stress. In the present study, different extracts obtained from plant food, plant by-products and dietary supplements, have been compared for their antioxidant properties before and after irradiation of 140 cGy, a dose absorbed during a hypothetical stay of three years in the space. All the dry extracts, characterized in terms of vitamin C and phenolic content, remained chemically unaltered and maintained their antioxidant capability after irradiation. Our results suggest the potential use of these extracts as nutraceuticals to protect humans from oxidative damages, even when these extracts must be stored in an environment exposed to cosmic radiations as in a space station.     

Clerodendrum viscosum: traditional uses,pharmacological activities and phytochemical constituents

Clerodendrum viscosum is widely distributed in tropical and subtropical regions of the world particularly in India. Extracts from different parts of the plant have been used elaborately in Ayurveda and Unani for treating different illness. Many phytochemicals were isolated from various parts of the plant, but their pharmacological potentials have not been largely explored. This review focuses on all these aspects of the plant keeping in view the cultural and traditional acceptability of its medicinal use. Its toxicological data are limited and require investigation to address for safety issues prior to recommendating for pharmaceutical use.     

Sigma-2 Receptor—A Potential Target for Cancer/Alzheimer’s Disease Treatment via Its Regulation of Cholesterol Homeostasis

The sigma receptors were classified into sigma-1 and sigma-2 receptor based on their different pharmacological profiles. In the past two decades, our understanding of the biological and pharmacological properties of the sigma-1 receptor is increasing; however, little is known about the sigma-2 receptor. Recently, the molecular identity of the sigma-2 receptor has been identified as TMEM97. Although more and more evidence has showed that sigma-2 ligands have the ability to treat cancer and Alzheimer’s disease (AD), the mechanisms connecting these two diseases are unknown. Data obtained over the past few years from human and animal models indicate that cholesterol homeostasis is altered in AD and cancer, underscoring the importance of cholesterol homeostasis in AD and cancer. In this review, based on accumulated evidence, we proposed that the beneficial roles of sigma-2 ligands in cancer and AD might be mediated by their regulation of cholesterol homeostasis.     

The young fruit of Citrus aurantium L. or Citrus sinensis Osbeck as a natural health food: A deep insight into the scientific evidence of its health benefits

Fruits are consumed as foods or medicines to supply people with nutrition or treat diseases. Zhishi, the dried young fruit of Citrus aurantium L. or Citrus sinensis Osbeck, is one of the most representative health food from the fruit of the Citrus genus. It is widely used in flavorings, canned food, beverages, and medicines because of its outstanding curative effects. The bidirectional regulating effect of Zhishi on the gastrointestinal tract for treating food stagnation or diarrhea has been confirmed. Its active ingredients, including synephrine and N-methyltyramine, have been used clinically as blood pressure boosting and anti-shock drugs. Flavonoids and alkaloids of Zhishi also make it potential weight loss and beauty products due to their definite effectiveness and safety. This paper intends to review the different therapeutic applications of Zhishi and the phytochemicals associated with its medicinal values. Besides, up-to-date information on its botany and analytical methods for the quality control of the medicine is supplied. To conclude, numerous independent research on Zhishi have been conducted in the past decades, but most of them are not deep enough in elucidating its scientific evidence of its health benefits. Further studies may unveil additional pharmacological activities and is beneficial to the mankind.     

Phytochemicals for the Prevention of Photocarcinogenesis

Ultraviolet (UV) exposure has an array of damaging effects and is the main cause of skin cancer in humans. Nonmelanoma skin cancer (NMSC), including basal cell carcinoma and squamous cell carcinoma, is the most common type of cancer. Incidence of NMSC has increased due to greater UV radiation, increased life expectancy and other changes in lifestyle; the annual cost of skin cancer treatment in the United States has increased concurrently to around eight billion dollars. Because of these trends, novel approaches to skin cancer prevention have become an important area of research to decrease skin cancer morbidity and defray the costs associated with treatment. Chemoprevention aims to prevent or delay the development of skin cancer through the use of phytochemicals. Use of phytochemicals as chemopreventive agents has gained attention due to their low toxicity and anticarcinogenic properties. Phytochemicals also exhibit antioxidant, anti‐inflammatory and antiproliferative effects which support their use as chemopreventive agents, particularly for skin cancer. Preclinical and human studies have shown that phytochemicals decrease UV‐induced skin damage and photocarcinogenesis. In this review article, we discuss the selected phytochemicals that may prevent or delay UV‐induced carcinogenesis and highlight their potential use for skin protection.     

Phytochemicals for prevention of solar ultraviolet radiation-induced damages

While solar light is indispensable for sustenance of life, excessive exposure can cause several skin-related disorders. The UV part of solar radiation, in particular, is linked to disorders ranging from mild inflammatory effects of the skin to as serious as causing several different types of cancers. Changes in lifestyle together with depletion in the atmospheric ozone layer during the last few decades have led to an increase in the incidence of skin cancer. Skin cancers consisting of basal and squamous cell carcinomas are especially linked to the UVB part of solar radiation. Reducing excessive exposure to solar radiation is desirable; however, as this approach is unavoidable, it is suggested that other novel strategies be developed to reduce the effects of solar radiation to skin. One approach to reduce the harmful effects of solar radiation is through the use of phytochemicals, an approach that is popularly known as "Photochemoprotection." In recent years many phytochemicals with potential antioxidant properties have been identified and found to be photoprotective in nature. We describe here some of the most popular phytochemicals being studied that have the potential to reduce the harmful effects associated with solar UV radiation.     

Isolation and in silico prediction of potential drug-like compounds from Anethum sowa L. root extracts targeted towards cancer therapy

Anethum sowa L. has been used as a spice herb in the Asian and European culinary systems to add flavour and taste. The studied plant has diverse folkloric medicinal value. Present study was designed to isolate phytochemicals from the hexane, chloroform and ethyl acetate extracts of the roots by various chromatographic techniques. Based on spectral analysis (IR, LC–MS, NMR) the isolated compounds were identified as physcione (1), β-sitosterol (2), stigmasterol (3), 2-oxo-3-propyl-2H-chromene-7-carboxylic acid (4), bergapten (5), 3-ethyl-7-hydroxy-2H-chromen-2-one (6) and graveolone (7). The mentioned compounds have been isolated for the first time from the roots part of the plant. Based on extensive literature review, physcione and bergapten were inferred to exhibit crucial bioactivities including inhibitory efficacy against various forms of cancer. Accordingly, in the present research approach molecular docking investigations of the isolated phytochemicals have been robustly executed with different oncogenes that have been reported to be actively involved in various forms of carcinoma. In silico investigations encompassing molecular docking analysis and drug-likeness profiling was executed to estimate the potential therapeutic tendencies of the phytochemicals targeted towards effective cancer therapy. Current investigation offers meaningful know-how pertaining to potential anticancer activities of the phytochemicals extracted from the roots of Anethum sowa L. and might open up new revenues towards effective drug development against cancer.     

Pharmacological Insights into Halophyte Bioactive Extract Action on Anti-Inflammatory,Pain Relief and Antibiotics-Type Mechanisms

The pharmacological activities in bioactive plant extracts play an increasing role in sustainable resources for valorization and biomedical applications. Bioactive phytochemicals, including natural compounds, secondary metabolites and their derivatives, have attracted significant attention for use in both medicinal products and cosmetic products. Our review highlights the pharmacological mode-of-action and current biomedical applications of key bioactive compounds applied as anti-inflammatory, bactericidal with antibiotics effects, and pain relief purposes in controlled clinical studies or preclinical studies. In this systematic review, the availability of bioactive compounds from several salt-tolerant plant species, mainly focusing on the three promising species Aster tripolium, Crithmum maritimum and Salicornia europaea, are summarized and discussed. All three of them have been widely used in natural folk medicines and are now in the focus for future nutraceutical and pharmacological applications.     

Asparagus racemosus: a review on its phytochemical and therapeutic potential

Asparagus racemosus (Willd.) is a widely found medicinal plant in tropical and subtropical parts of India. The therapeutic applications of this plant have been reported in Indian and British Pharmacopoeias and in traditional system of medicine, such as Ayurveda, Unani and Siddha. The crude, semi-purified and purified extracts obtained from different parts of this plant have been useful in therapeutic applications. Numerous bioactive phytochemicals mostly saponins and flavonoids have been isolated and identified from this plant which are responsible alone or in combination for various pharmacological activities. This review aims to give a comprehensive overview of traditional applications, current knowledge on the phytochemistry, pharmacology and overuse of A. racemosus.     

Inhibitory Role of Berberine,an Isoquinoline Alkaloid,on NLRP3 Inflammasome Activation for the Treatment of Inflammatory Diseases

The pyrin domain-containing multiprotein complex NLRP3 inflammasome, consisting of the NLRP3 protein, ASC adaptor, and procaspase-1, plays a vital role in the pathophysiology of several inflammatory disorders, including neurological and metabolic disorders, chronic inflammatory diseases, and cancer. Several phytochemicals act as promising anti-inflammatory agents and are usually regarded to have potential applications as complementary or alternative therapeutic agents against chronic inflammatory disorders. Various in vitro and in vivo studies have reported the anti-inflammatory role of berberine (BRB), an organic heteropentacyclic phytochemical and natural isoquinoline, in inhibiting NLRP3 inflammasome-dependent inflammation against many disorders. This review summarizes the mechanism and regulation of NLRP3 inflammasome activation and its involvement in inflammatory diseases, and discusses the current scientific evidence on the repressive role of BRB on NLRP3 inflammasome pathways along with the possible mechanism(s) and their potential in counteracting various inflammatory diseases.     

Novel Marine Secondary Metabolites Worthy of Development as Anticancer Agents: A Review

Secondary metabolites from marine sources have a wide range of biological activity. Marine natural products are promising candidates for lead pharmacological compounds to treat diseases that plague humans, including cancer. Cancer is a life-threatening disorder that has been difficult to overcome. It is a long-term illness that affects both young and old people. In recent years, significant attempts have been made to identify new anticancer drugs, as the existing drugs have been useless due to resistance of the malignant cells. Natural products derived from marine sources have been tested for their anticancer activity using a variety of cancer cell lines derived from humans and other sources, some of which have already been approved for clinical use, while some others are still being tested. These compounds can assault cancer cells via a variety of mechanisms, but certain cancer cells are resistant to them. As a result, the goal of this review was to look into the anticancer potential of marine natural products or their derivatives that were isolated from January 2019 to March 2020, in cancer cell lines, with a focus on the class and type of isolated compounds, source and location of isolation, cancer cell line type, and potency (IC₅₀ values) of the isolated compounds that could be a guide for drug development.     

The Effects of Capsaicin on Gastrointestinal Cancers

Gastrointestinal (GI) cancers are a group of diseases with very high positions in the ranking of cancer incidence and mortality. While they show common features regarding the molecular mechanisms involved in cancer development, organ-specific pathophysiological processes may trigger distinct signaling pathways and intricate interactions with inflammatory cells from the tumoral milieu and mediators involved in tumorigenesis. The treatment of GI cancers is a topic of increasing interest due to the severity of these diseases, their impact on the patients’ survivability and quality of life, and the burden they set on the healthcare system. As the efficiency of existing drugs is hindered by chemoresistance and adverse reactions when administered in high doses, new therapies are sought, and emerging drugs, formulations, and substance synergies are the focus of a growing number of studies. A class of chemicals with great potential through anti-inflammatory, anti-oxidant, and anti-tumoral effects is phytochemicals, and capsaicin in particular is the subject of intensive research looking to validate its position in complementing cancer treatment. Our paper thoroughly reviews the available scientific evidence concerning the effects of capsaicin on major GI cancers and its interactions with the molecular pathways involved in the course of these diseases.     

Aquilaria Species (Thymelaeaceae) Distribution,Volatile and Non-Volatile Phytochemicals,Pharmacological Uses,Agarwood Grading System,and Induction Methods

Agarwood is a highly valuable fragrant wood of Aquilaria spp. (Thymelaeaceae) which has been widely utilized in traditional medicine, religious rites, and cultural activities. This study summarizes a review on the identification of Aquilaria cultivars, volatile and non-volatile phytochemicals, pharmacological uses, and agarwood grading system to determine its quality, and different agarwood induction methods. Due to the highly demanding and depleted natural resources, the research on agarwood is still insufficient, and it has broad research and development prospects in many industries. However, due to the significant scientific nature of agarwood application, developing high-quality products and drugs from agarwood have become highly important, while no one has discussed in detail the phytochemicals uses and provided a summary until now. The main phytochemicals of agarwood include terpenoids, dominated by sesquiterpenes. For centuries, terpenoids have been used in traditional Chinese medicine and have been shown to possess various pharmacological properties, including bacteriostatic, antibacterial, sedation, analgesia, anti-inflammation, anti-asthmatic, hypoglycemic, antidepressant, and many others. Alongside biological activity screening, phytochemical advances and pharmacological research have also made certain progress. Therefore, this review discusses the research progress of agarwood in recent years and provides a reference basis for further study of Aquilaria plants and agarwood.     

常见针叶行道树化学成分研究进展

根据近20年文献报道,针叶行道树化学成分的研究在国内已经逐渐成为热点,其含有的挥发油、油脂、黄酮以及莽草酸具有各自不同的作用,大部分可以用于医治疾病。作者按照化学分类综述了国内主要针叶行道树的化学成分及其药理活性,为进一步研究针叶行道树的化学成分提供了参考。     

Phenylpropanoids in radioregulation: double edged sword

Radiotherapy, frequently used for treatment of solid tumors, carries two main obstacles including acquired radioresistance in cancer cells during radiotherapy and normal tissue injury. Phenylpropanoids, which are naturally occurring phytochemicals found in plants, have been identified as potential radiotherapeutic agents due to their anti-cancer activity and relatively safe levels of cytotoxicity. Various studies have proposed that these compounds could not only sensitize cancer cells to radiation resulting in inhibition of growth and cell death but also protect normal cells against radiation-induced damage. This review is intended to provide an overview of recent investigations on the usage of phenylpropanoids in combination with radiotherapy in cancer treatment.     

Rosa platyacantha Schrenk from Kazakhstan—Natural Source of Bioactive Compounds with Cosmetic Significance

Plants belonging to the Rosa genus are known for their high content of bioactive molecules and broad spectrum of healing and cosmetic activities. Rosa platyacantha Schrenk is a wild-type species abundant in the mountainous regions of Kazakhstan. The phytochemical composition as well as the bioactivity of R. platyacantha extracts have not been fully investigated to date. In this study, various parts of R. platyacantha plant, collected in Almaty region, Kazakhstan, were used to prepare five hydroalcoholic extracts (R1–R5). The extracts were compared for the content of phytochemicals and selected biological activities, which are important for the potential cosmetic application of R. platyacantha. Extract R3, prepared from flower buds, showed the most significant antioxidant and tyrosinase inhibitory potential, decreasing the monophenolase and diphenolase activities of tyrosinase. Extract R3 showed also collagenase inhibitory activity and cytotoxicity against human melanoma cells A375, being less cytotoxic for noncancerous skin keratinocytes HaCaT. Analysis of fractions E and F, obtained from R3 extracts, revealed that quercetin, kaempferol, rutin, and their derivatives are more likely responsible for the tyrosinase inhibitory properties of R. platyacantha extracts.