Current Pharmaceutical Design - Volume 27, Issue 4, 2021

Nature always remains an inexhaustible source of treasures for mankind. It remains a mystery for every challenge until the completion of the challenge. While we talk about the complicated health issues, nature offers us a great variety of chemical scaffolds and their various moieties packed in the form of natural products e.g., plants, microorganisms (fungi, algae, protozoa), and terrestrial vertebrates and invertebrates. This review article is an update about jaceosidin, a bioactive flavone, from genus Artemisia. This potentially active compound exhibits a variety of pharmacological activities including anti-inflammatory, anti-oxidant, anti-bacterial, antiallergic and anti-cancer activities. The bioactivities and the therapeutic action of jaceosidin, especially the modulation of different cell signaling pathways (ERK1/2, NF-ΚB, PI3K/Akt and ATM-Chk1/2) which become deregulated in various pathological disorders, have been focused here. The reported data suggest that the bioavailability of this anti-cancer compound should be enhanced by utilizing various chemical, biological and computational techniques. Moreover, it is recommended that researchers and scientists should work on exploring the mode of action of this particular flavone to precede it further as a potent anti-cancer compound.

Cancer, global havoc, is a group of debilitating diseases that strikes family as well as society. Cancer cases are drastically increasing these days. Despite many therapies and surgical procedures available, cancer is still difficult to control due to limited effective therapies or targeted therapies. Natural products can produce lesser side effects to the normal cells, which are the major demerit of chemotherapies and radiation. Wogonin, a natural product extracted from the plant, Scutellaria baicalensis has been widely studied and found with a high caliber to tackle most of the cancers via several mechanisms that include intrinsic as well as extrinsic apoptosis signaling pathways, carcinogenesis diminution, telomerase activity inhibition, metastasis inhibition in the inflammatory microenvironment, anti-angiogenesis, cell growth inhibition and arrest of the cell cycle, increased generation of H2O2 and accumulation of Ca²⁺ and also as an adjuvant along with anticancer drugs. This article discusses the role of wogonin in various cancers, its synergism with various drugs, and the mechanism by which wogonin controls tumor growth.

Apigenin is an edible flavonoid widely distributed in natural plants, including most vegetables and fruits. Previous studies have revealed that apigenin possesses multiple biological functions by demonstrating antiinflammatory, anti-oxidative, anti-bacterial, anti-viral, anti-tumor and cardiovascular protective effects. Furthermore, recent progressions have disclosed a novel perspective of the anti-cancer roles of apigenin through its immunoregulatory functions. With the rapid progression of the groundbreaking strategies being developed for cancer immunotherapy, its immunoregulatory roles are being recognized as intriguing features of the multifaceted apigenin. However, the current understanding of this emerging role of apigenin still remains limited. Therefore, in the present review, recent advances on the immunoregulatory properties of apigenin in various diseases with a special focus on neoplasm, are summarized. Clinical strategies of cancer immunotherapy are briefly introduced and findings on apigenin linked to immunoregulatory roles in immunotherapy-associated aspects are brought together. The bioactivity, bioavailability, toxicity and potential of apigenin, to be considered as a therapeutic agent in anti-tumor immunotherapy, is discussed. Disclosed molecular mechanisms underlying the immunoregulatory roles of apigenin in cancer immunotherapy are also summarized. Based on findings from the literature, apigenin has the potential to serve as a prospective adjuvant for anti-cancer immunotherapy and warrants further investigations.

Background: The increasing interests on the healing properties of medicinal plants have led to a paradigm shift from the use of synthetic drug to the search of natural medicines for the treatment and management of several diseases. Like other phenolics flavonoids have been continuously explored for their medicinal benefits, with their potent antioxidant activity being a major interest. Kolaviron (KVN) is a biflavonoid isolated from Garcinia kola Heckel, which has been reported for its potent antioxidant and anti-inflammatory properties. These properties have been explored in several disease models including reproductive toxicity, cardiotoxicity, diabetes mellitus, gastrotoxicity and hepatotoxicity. Objectives: The present study was aimed to review the reported medicinal properties of KVN in order to provide some guidelines and direction to researchers on KVN research. Methods: A literature search was conducted with the aim of identifying peer-reviewed published data on KVN and their biological activities. Different academic and/or scientific search engines were utilized including but not limited to Google Scholar, PubMed, ScienceDirect and so on. Results: Among all the studied disease models obtained from the literatures, the effect of KVN on reproductive toxicity was the most studied as it represented 25% of all the studies, followed by neuroprotective, cardioprotective and hepatoprotective activities of Kolaviron. From our identified studies, KVN has been shown to have antidiabetic, cardioprotective, neuroprotective, hematoprotective, nephroprotective, gastroprotective, hepatoprotective activities. KVN also has effects on malaria and reproductive health, which can be explored for novel drug and nutraceutical developments for related ailments. Unfortunately, while toxicity data are lacking, most studies are limited to in vitro and/or in vivo models, which may impede translation in this area of research. Conclusion: Based on data gathered from the literature search, it is evident that KVN possesses numerous health benefits, which can be attributed to its potent antioxidant and anti-inflammatory activities. However, more studies are required in this area of research to validate the medicinal value of kolaviron, which may positively influence the economic value of plant, Garcinia kola.

Flavonoids represent a large diverse group of natural products that are used as a traditional medicine against various infectious diseases. They possess many biological activities including antimicrobial, antioxidant, anti-inflammatory, anti-cancer and anti-diabetic activities. Commercially, flavonoids are mainly obtained from plants, however, several challenges are faced during their extraction. Microorganisms have been known as natural sources of a wide range of bioactive compounds including flavonoids. Actinobacteria are the most prolific group of microorganisms for the production of bioactive secondary metabolites, thus facilitating the production of flavonoids. The screening programs for bioactive compounds revealed the potential application of actinobacteria to produce flavonoids with interesting biological activities, especially anticancer activities. Since marine actinobacteria are recognized as a potential source of novel anticancer agents, they are highly expected to be potential producers of anticancer flavonoids with unusual structures and properties. In this review, we highlight the production of flavonoids by actinobacteria through classical fermentation, engineering of plant biosynthetic genes in a recombinant actinobacterium and the de novo biosynthesis approach. Through these approaches, we can control and improve the production of interesting flavonoids or their derivatives for the treatment of cancer.

Flavonoids, the main class of polyphenols, are characterized by the presence of 2-phenyl-benzo-pyrane nucleus. They are found in rich quantities in citrus fruits. Citrus flavonoids are classified into flavanones, flavones, flavonols, polymethoxyflavones and anthocyanins (found only in blood oranges). Flavanones are the most abundant flavonoids in citrus fruits. In many situations, there are structure-function relationships. Due to their especial structures and presence of many hydroxyls, polymethoxies and glycoside moiety, the flavonoids have an array of multiple biological and pharmacological activities. This article provides an updated overview of the differences in chemical structures of the classes and members of citrus flavonoids and their benefits in health and diseases. The review article also sheds light on the mechanisms of actions of citrus flavonoids in the treatment of different diseases, including arthritis, diabetes mellitus, cancer and neurodegenerative disorders as well as liver, kidney and heart diseases. The accumulated and updated knowledge in this review may provide useful information and ideas in the discovery of new strategies for the use of citrus flavonoids in the protection, prevention and therapy of diseases.

Neurological diseases bring great mental and physical torture to the patients, and have long-term and sustained negative effects on families and society. The attention to neurological diseases is increasing, and the improvement of the material level is accompanied by an increase in the demand for mental level. The p75 neurotrophin receptor (p75NTR) is a low-affinity neurotrophin receptor and involved in diverse and pleiotropic effects in the developmental and adult central nervous system (CNS). Since neurological diseases are usually accompanied by the regression of memory, the pathogenesis of p75NTR also activates and inhibits other signaling pathways, which has a serious impact on the learning and memory of patients. The results of studies shown that p75NTR is associated with LTP/LTD-induced synaptic enhancement and inhibition, suggest that p75NTR may be involved in the progression of synaptic plasticity. And its proapoptotic effect is associated with activation of proBDNF and inhibition of proNGF, and TrkA/p75NTR imbalance leads to pro-survival or proapoptotic phenomena. It can be inferred that p75NTR mediates apoptosis in the hippocampus and amygdale, which may affect learning and memory behavior. This article mainly discusses the relationship between p75NTR and learning memory and associated mechanisms, which may provide some new ideas for the treatment of neurological diseases.

Mucoadhesive formulations have been demonstrated to result in efficient drug delivery systems with advantages over existing systems such as increased local retention and sustained drug release via adhesiveness to mucosal tissues. The controlled release of colon-targeted, orally administered drugs has recently attracted a number of studies investigating mucoadhesive systems. Consequently, substantial designs, from mucoadhesive cores to shells of particles, have been studied with promising applications. This review will provide an overview of specific strategies for developing mucoadhesive systems for colon-targeted oral delivery with controlled drug release, including mucoadhesive matrices, cross-linked mucoadhesive microparticles, coatings and mucoadhesive nanoparticles. The understanding of the basic principle of these designs and advanced formulations throughout will lead to the development of products with efficient drug delivery at the colon for therapies for different diseases.

Purpose: Improving hypertension management is still one of the biggest challenges in public health worldwide. Existing guidelines do not reach a consensus on the optimal Blood Pressure (BP) target. Therefore, how to effectively manage hypertension based on individual characteristics of patients, combined with the pharmacological and non-pharmacological approach, has become a problem to be urgently considered. Methods: Reports published in PubMed that covered Pharmacological and Non-Pharmacological Approaches in subjects taking hypertension management were reviewed by the group independently and collectively. Practical recommendations for hypertension management were established by the panel. Results: Pharmacological mechanism, action characteristics, and main adverse reactions varied across different pharmacological agents, and patients with hypertension often require a combination of antihypertensive medications to achieve the target BP range. Non-pharmacological treatment provides an additional effective method for improving therapy adherence and long-term BP control, thus reducing the risk of cardiovascular diseases, and slowing down the progression of the disease. Conclusion: This review summarizes the available literature on the most convincing guideline principles, pharmacological treatment, biotechnology interference, interventional surgical treatment, managing hypertension with technical means of big data, Artificial Intelligence and Behavioral Intervention, as well as providing future directions, for facilitating Current and Developing knowledge into clinical implementation.

Nanomedicines exhibit unbelievable capability in overcoming the hurdles faced in biological applications. Carbon nanotubes (CNTs), graphene-family nanomaterials and fullerenes are a class of engineered nanoparticles that have emerged as a new option for possible use in drug/gene delivery for life-threatening diseases. Their adaptability to pharmaceutical applications has opened new vistas for biomedical applications. Successful applications of this family of engineered nanoparticles in various fields may not support their use in medicine due to inconsistent data on toxicity as well as the lack of a centralized toxicity database. Inconsistent toxicological studies and lack of mechanistic understanding have been the reasons for limited understanding of their toxicological aspects. These nanoparticles, when underivatized or pristine, are considered as safe, however less reactive. The derivatized forms or functionalization changes their chemistry significantly to modify their biological effects including toxicity. They can cause acute and long term injuries in tissues by penetration through the the blood-air barrier, blood-alveolus barrier, blood-brain barrier, and blood-placenta barrier. and by accumulating in the lung, liver, and spleen . The toxicological effects are manifested through inflammatory response, DNA damage, apoptosis, autophagy and necrosis. Other factors that largely influence the toxicity of carbon nanotubes, graphenes and fullerenes are the concentration, functionalization, dimensional and surface topographical factors. Thus, a better understanding of the toxicity profile of CNTs, graphene-family nanomaterials and fullerenes in humans, animals and the environment is of significant importance, to improve their biological safety, to facilitate their wide biological application and for the successful commercial application. The exploration of appropriate cell lines to investigate specific receptors and intracellular targets as well as chronic toxicity beyond the proof-of-concept is required.

Background: The antagonistic relationship between adenosine monophosphate-activated protein kinase (AMPK) and phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling play a vital role in cancer development. The anti-cancer effects of berberine have been reported as a main component of the traditional Chinese medicine Rhizoma coptidis, although the roles of these signaling pathways in these effects have not been systematically reviewed. Methods: We searched the PubMed database for studies with keywords including [“berberine”] and [“tumor” or “cancer”] and [“AMPK”] or [“AKT”] published between January 2010 and July 2020, to elucidate the roles of the AMPK and PI3K/AKT pathways and their upstream and downstream targets in the anti-cancer effects of berberine. Results: The anti-cancer effects of berberine include inhibition of cancer cell proliferation, promotion of apoptosis and autophagy in cancer cells, and prevention of metastasis and angiogenesis. The mechanism of these effects involves multiple cell kinases and signaling pathways, including activation of AMPK and forkhead box transcription factor O3a (FOXO3a), accumulation of reactive oxygen species (ROS), and inhibition of the activity of PI3K/AKT, rapamycin (mTOR) and nuclear factor-ΚB (NF-ΚB). Most of these mechanisms converge on regulation of the balance of AMPK and PI3K/AKT signaling by berberine. Conclusion: This evidence supports the possibility that berberine is a promising anti-cancer natural product, with pharmaceutical potential in inhibiting cancer growth, metastasis and angiogenesis via multiple pathways, particularly by regulating the balance of AMPK and PI3K/AKT signaling. However, systematic preclinical studies are still required to provide scientific evidence for further clinical studies.

Background: Long non-coding RNAs (LncRNAs), with the length of over 200 nucleotides, that originate from intergenic, antisense, or promoter-proximal regions, are a large family of RNAs that lack coding capacity. Emerging evidences illustrated that LncRNAs played significant roles in a variety of cellular functions and biological processes in profuse human diseases, especially in cancers. Cancer susceptibility candidate 9 (CASC9), as a member of the LncRNAs group, firstly found its oncogenic function in esophageal cancer. In the following recent studies, a growing amount of human malignancies are verified to be correlated with CASC9, most of which are derived from the squamous epithelium tissue. This present review attempts to highlight the latest insights into the expression, functional roles, and molecular mechanisms of CASC9 in different human malignancies. Methods: In this review, the latest findings related to the pathophysiological processes of CASC9 in human cancers were summarized and analyzed, and the associated studies collected in systematic retrieval of PubMed used lncRNA and CASA9 as keywords. Results: CASC9 expression is identified to be aberrantly elevated in a variety of malignancies. The over-expression of CASC9 has been suggested to accelerate cell proliferation, migration, cell growth and drug resistance of cancer cells, while depressing cell apoptosis, revealing its role as an oncogene. Moreover, the current review demonstrated CASC9 as closely related to the neoplastic transformation of squamous epithelial cells and squamous metaplasia in non-squamous epithelial tissues. Finally, we discuss the limitations and tremendous diagnostic/ therapeutic potential of CASC9 in various human cancers. Conclusion: Long non-coding RNA CASC9 likely serve as useful disease biomarkers or therapeutic targets which be effectively applied in the treatment of different kinds of cancers.