Piperlongumine: the amazing amide alkaloid from Piper in the treatment of breast cancer.

Piperlongumine (PL), an alkaloid found primarily in the fruits and roots of the plant Piper longum L. (Piperaceae), is a natural compound that exhibits potent activity against various cancer cell proliferation. The most frequently caused malignancy in women globally, breast cancer (BC), has been demonstrated to be significantly inhibited by PL. Apoptosis, cell cycle arrest, increased ROS generation, and changes in the signalling protein's expression are all caused by the numerous signalling pathways that PL impacts. Since BC cells resist conventional chemotherapeutic drugs (doxorubicin, docetaxel etc.), researchers have shown that the drugs in combination with PL can exhibit a synergistic effect, greater than the effects of the drug or PL alone. Recently, techniques for drug packaging based on nanotechnology have been employed to improve PL release. The review has presented an outline of the chemistry of PL, its molecular basis in BC, its bioavailability, toxicity, and nanotechnological applications. An attempt to understand the future prospects and direction of research about the compound has also been discussed.

Ligand-based active targeting strategies for cancer theranostics.

In the past decades, for the intermediate or advanced cancerous stages, preclinical and clinical applications of nanomedicines in cancer theranostics have been extensively studied. Nevertheless, decreased specificity and poor targeting efficiency with low target concentration of theranostic are the major drawbacks of nanomedicine in employing clinical substitution over conventional systemic therapy. Consequently, ligand decorated nanocarrier-mediated targeted drug delivery system can transcend the obstructions through their enhanced retention activity and increased permeability with effective targeting. The highly efficient and specific nanocarrier-mediated ligand-based active therapy is one of the novel and promising approaches for delivery of the therapeutics for different cancers in recent years to restrict various cancer growth in vivo without harming healthy cells. The article encapsulates the features of nanocarrier-mediated ligands in augmentation of active targeting approaches of various cancers and summarizes ligand-based targeted delivery systems in treatment of cancer as plausible theranostics.

Mangiferin: the miraculous xanthone with diverse pharmacological properties.

Mangiferin (1,3,6,7-tetrahydroxy-2-[3,4,5-trihydroxy-6-(hydroxymethyl) oxan-2-yl] xanthen-9-one) is a bioactive component derived primarily from the mango tree. Belonging to the Xanthone family, its structure allows it to engage with a variety of pharmacological targets. The symmetric linked core of xanthones has a heterogeneous biogenetic background. The carbon atoms are designated in a biochemical order, which reveals the reason of ring A (C1-C4) being referred to as acetate originated, and ring B (C5-C8) is referred to as shikimate originated. The antibacterial, hypocholesterolemic, antiallergic, cardiotonic, antidiabetic, anti-neoplastic, neuroprotective, antioxidant and immunomodulatory properties have all been demonstrated for the secondary metabolite. This study assessed and explained the important medical properties of mangiferin available in published literature, as well as its natural source, biosynthesis, absorption and bioavailability; multiple administration routes; metabolism; nanotechnology for enhanced efficacy of mangiferin and its toxicity, to aid the anticipated on-going potential of mangiferin as a novel diagnostic treatment.

Unravelling the pharmacological properties of cryptolepine and its derivatives: a mini-review insight.

Cryptolepine (1,5-methyl-10H-indolo[3,2-b]quinoline), an indoloquinoline alkaloid, found in the roots of Cryptolepis sanguinolenta (Lindl.) Schltr (family: Periplocaceae), is associated with the suppression of cancer and protozoal infections. Cryptolepine also exhibits anti-bacterial, anti-fungal, anti-hyperglycemic, antidiabetic, anti-inflammatory, anti-hypotensive, antipyretic, and antimuscarinic properties. This review of the latest research data can be exploited to create a basis for the discovery of new cryptolepine-based drugs and their analogues in the near future. PubMed, Scopus, and Google Scholar databases were searched to select and collect data from the existing literature on cryptolepine and their pharmacological properties. Several in vitro studies have demonstrated the potential of cryptolepine A as an anticancer and antimalarial molecule, which is achieved through inhibiting DNA synthesis and topoisomerase II. This review summarizes the recent developments of cryptolepine pharmacological properties and functional mechanisms, providing information for future research on this natural product.

Barbaloin: an amazing chemical from the 'wonder plant' with multidimensional pharmacological attributes.

Aloe vera (L.) Burm.f. is nicknamed the 'Miracle plant' or sometimes as the 'Wonder plant'. It is a plant that has been used since ancient times for the innumerable health benefits associated with it. It is one of the important plants that has its use in conventional medicinal treatments. It is a perennial succulent, drought-tolerant member of the family Asphodelaceae. There are scores of properties associated with the plant that help in curing various forms of human ailments. Extracts and gels obtained from plants have been shown to be wonderful healers of different conditions, mainly various skin problems. Also, this plant is popular in the cosmetics industry. The underlying properties of the plant are now mainly associated with the natural phytochemicals present in the plant. Diverse groups of phytoingredients are found in the plant, including various phenolics, amino acids, sugars, vitamins, and different other organic compounds, too. One of the primary ingredients found in the plant is the aloin molecule. It is an anthraquinone derivative and exists as an isomer of Aloin A and Aloin B. Barbaloin belonging to the first group is a glucoside of the aloe-emodin anthrone molecule. Various types of pharmacological properties exhibited by the plant can be attributed to this chemical. Few significant ones are antioxidant, anti-inflammatory, anti-diabetic, anti-cancer, anti-microbial, and anti-viral, along with their different immunity-boosting actions. Recently, molecular coupling studies have also found the role of these molecules as a potential cure against the ongoing COVID-19 disease. This study comprehensively focuses on the numerous pharmacological actions of the primary compound barbaloin obtained from the Aloe vera plant along with the mechanism of action and the potent application of these natural molecules under various conditions.

CRISPER/Cas in Plant Natural Product Research: Therapeutics as Anticancer and other Drug Candidates and Recent Patents.

BACKGROUND: Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR- associated9 (Cas9) endonuclease system is a facile, highly efficient and selective site-directed mutagenesis tool for RNA-guided genome-editing. CRISPR/Cas9 genome-editing strategy uses designed guide-RNAs that recognizes a 3 base-pair protospacer adjacent motif (PAM) sequence in the target-DNA. CRISPR/Cas-editing tools have mainly been employed in crop plants in relation to yield and stress tolerance. However, the immense potential of this technology has not yet been fully utilized in medicinal plants in deciphering or modulating secondary metabolic pathways producing therapeutically active phytochemicals against cancer and other diseases. OBJECTIVE: The present review elucidates the use of CRISPR-Cas9 as a promising genome-editing tool in plants and plant-derived natural products with anticancer and other therapeutic applications. It also includes recent patents on the therapeutic applications of CRISPR-CAS systems implicated to cancer and other human medical conditions. METHODS: Popular search engines, such as PubMed, Scopus, Google Scholar, Google Patents, Medline, ScienceDirect, SpringerLink, EMBASE, Mendeley, etc., were searched in order to retrieve literature using relevant keywords viz. CRISPER/Cas, plant natural product research, anticancer, therapeutics, etc., either singly or in various combinations. RESULTS: Retrieved citations and further cross-referencing among the literature have resulted in a total number of 71 publications and 3 patents are being cited in this work. Information presented in this review aims to support further biotechnological and clinical strategies to be carried using CRISPER/ Cas mediated optimization of plant natural products against cancer and an array of other human medical conditions. CONCLUSION: Off late, knock-in and knock-out, point mutation, controlled tuning of gene-expression and targeted mutagenesis have enabled the versatile CRISPR/Cas-editing device to engineer medicinal plants' genomes. In addition, by combining CRISPR/Cas-editing tool with next-generation sequencing (NGS) and various tools of system biology, many medicinal plants have been engineered genetically to optimize the production of valuable bioactive compounds of industrial significance.

Withania somnifera (L.) Dunal (Ashwagandha): A comprehensive review on ethnopharmacology, pharmacotherapeutics, biomedicinal and toxicological aspects.

Withania somnifera (L.) Dunal (Solanaceae) has been used as a traditional Rasayana herb for a long time. Traditional uses of this plant indicate its ameliorative properties against a plethora of human medical conditions, viz. hypertension, stress, diabetes, asthma, cancer etc. This review presents a comprehensive summary of the geographical distribution, traditional use, phytochemistry, and pharmacological activities of W. somnifera and its active constituents. In addition, it presents a detailed account of its presence as an active constituent in many commercial preparations with curative properties and health benefits. Clinical studies and toxicological considerations of its extracts and constituents are also elucidated. Comparative analysis of relevant in-vitro, in-vivo, and clinical investigations indicated potent bioactivity of W. somnifera extracts and phytochemicals as anti-cancer, anti-inflammatory, apoptotic, immunomodulatory, antimicrobial, anti-diabetic, hepatoprotective, hypoglycaemic, hypolipidemic, cardio-protective and spermatogenic agents. W. somnifera was found to be especially active against many neurological and psychological conditions like Parkinson's disease, Alzheimer's disease, Huntington's disease, ischemic stroke, sleep deprivation, amyotrophic lateral sclerosis, attention deficit hyperactivity disorder, bipolar disorder, anxiety, depression, schizophrenia and obsessive-compulsive disorder. The probable mechanism of action that imparts the pharmacological potential has also been explored. However, in-depth studies are needed on the clinical use of W. somnifera against human diseases. Besides, detailed toxicological analysis is also to be performed for its safe and efficacious use in preclinical and clinical studies and as a health-promoting herb.

Bacosides from Bacopa monnieri extract: An overview of the effects on neurological disorders.

From ancient history, complementary and alternative medicines have played a significant role as holistic therapeutic treatments of various human diseases including cancer, diabetes, neurological diseases, and skin problems. One Indian medicinal plant (herb), Bacopa monnieri has been used in many parts of the world as such medicine, particularly for the treatment of various neurological disorders. It is well known as a potent "tonic for the human brain," which serves as a memory enhancer. Multiple studies proved that this herb contains a plethora of potential bioactive, phytochemical compounds with synergistic properties. The main purpose of the present review is to shed light on the use of Bacopa monnieri and its active principles (bacosides) in the management of neurological disorders. Furthermore, the signaling pathways modulated by bacosides have been critically discussed in this review. Moreover, we have critically summarized the present knowledge of this perennial creeping herb based upon the literature mining from different scientific engines.

Bibenzyls and bisbybenzyls of bryophytic origin as promising source of novel therapeutics: pharmacology, synthesis and structure-activity.

BACKGROUND: The amphibian, non-vascular, gametophyte-dominant, bio-indicator class, bryophytes; with their wide ranges of habitat have attained importance due to their promising medicinal attributions and therapeutic role; mostly aided by presence of aromatic bibenzyl and bisbybenzyl class of compounds. Bibenzyls are steroidal ethane derivatives, resembling the structural moiety of bioactive dihydro-stilbenoids or iso-quinoline alkaloids. These stress triggered secondary metabolites are the by-products of the flavonoid biosynthetic pathway. Different classes of bryophytes (Bryophyta, Marchantiophyta and Anthocerotophyta) possess different subtypes of bibenzyls and dimeric bisbibenzyls. Among the liverwort, hornwort and mosses, former one is mostly enriched with bibenzyl type constituents as per the extensive study conducted for phytochemical deposit. Considering macrocyclic and acyclic group of bibenzyls and bisbybenzyls, generally marchantin type compounds are reported vividly for significant biological activity that includes neuro-nephro-cardio-protection besides anti-allergic, anti-microbial, anti-apoptotic and cytotoxic activities studied on in-vitro and in-vivo models or on cell lines. RESULT: The critical analysis of reported chemical and pharmaceutical attributions of bibenzyls and bis-bibenzyls yielded detailed report on this compound class along with their application, mode of action, natural source, techniques of synthesis, extraction procedure, isolation and characterization. Further, the structure activity relationship studies and bioactivity of bibenzyls derived from non-bryophytic origin were also summarized. CONCLUSION: This review encompasses prospective biological application of botanical reservoir of this primarily ignored, primeval land plant group where recent technical advances has paved the way for qualitative and quantitative isolation and estimation of novel compounds as well as marker components to study their impact on environment, as bio-control agents and as key leads in future drug designing. Graphical abstract.

A review on antimicrobial botanicals, phytochemicals and natural resistance modifying agents from Apocynaceae family: Possible therapeutic approaches against multidrug resistance in pathogenic microorganisms.

Accelerated emergence of drug- resistant pathogenic microbes, their unbeatable virulence and a gradual loss of efficacy of currently used antimicrobial agents over the last decade, have expanded the scope of herbal medicine to combat this emerging challenge to have a wide spectrum of activity to develop effective medicines with lesser untoward side effects. Plant-based natural products should be of utmost interest to today's pharmaceutical industries since they are a primary source of new chemical entities directed at new drug targets. Apocynaceae or 'Dogbane' family has attained a global reputation as a source of some life-saving plant-derived products and novel compounds. Members of this family have also been extensively investigated against several nosocomial pathogenic microbes through in vitro and in vivo experimental settings. Several plant-derived components obtained from members of this family have also exhibited remarkable microbial growth inhibitory properties. Popular and widely accepted international databases such as PubMed, Science Direct, ResearchGate, Scopus, Google Scholar, JSTOR and more were searched using the various search strings such as Apocynaceae, antimicrobials, multidrug resistance, resistance modifying agents and pathogenic microorganisms were used in various combinations to retrieve several citations related to the topic. The current review encompasses recent developments in experimental studies and phytochemical analyses which correlates with antimicrobial efficacy of selected Apocynaceous plants along with synergistic mechanism and structural details. The present review recognizes and leverages the importance of Apocynaceae plants, which could be of significant interest in the development of more effective and less toxic antimicrobial drugs which may surmount multidrug resistance. Three different paradigm models harnessing clinical antimicrobial resistance (AMR) including the plant family Apocynaceae, Gram-positive and Gram-negative bacterial species have been broadly discussed in this review. In a nutshell, the present review represents a comprehensive account on the antimicrobials and resistance modifying agents obtained from the members of the plant family Apocynaceae and derived phytochemicals. It also gives an insight into the underlying mode of action of these phytochemicals against an array of pathogenic bacteria, their mechanism of antibiosis, plant parts from which the phytochemicals were isolated or the extracts was prepared with a critical discussion on the botanically-derived antibiotics as a template for antimicrobial drug development.

Indian Sarsaparilla (Hemidesmus indicus): Recent progress in research on ethnobotany, phytochemistry and pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: Hemidesmus indicus (L.) R. Br. ex Schult. (Apocynaceae) is widely used in traditional medicine in the different parts of the Indian subcontinent due to the various biological activities attributed to its different parts, especially the roots. It has traditionally been used for treating snakebites, scorpion stings, diabetes, urinary diseases, dyspnea, menorrhagia, oligospermia, anorexia, fever, abdominal colic and pain, dysentery, diarrhea, cough, rheumatism, headache, inflammation, pyrosis, skin diseases, leprosy, sexually transmitted diseases and cancer. In Ayurveda, the plant is used in the treatment of bone-loss, low body weight, fever, stress, topical wound and psoriasis. Besides, Ayurvedic literature also depicts its use as anti-atherogenic, anti-spasmodic, memory enhancing, immunopotentiating and anti-inflammatory agents. AIM OF THE STUDY: In this review, we aim to present a comprehensive update on the ethnopharmacology, phytochemistry, specific pharmacology, and toxicology of H. indicus and its bioactive metabolites. Possible directions for future research are also outlined in brief. MATERIALS AND METHODS: Popular and widely used international databases such as PubMed, Scopus, Science Direct, Google Scholar and JSTOR were searched and traditional literature were consulted using the various search strings to retrieve a number of citations related to the ethnopharmacology, biological activity, toxicology, quality control and phytochemistry of H. indicus. All studies on the ethnobotany, phtochemistry, pharmacology, and toxicology of the plant up to 2019 were included in this review. RESULTS: H. indicus has played an important role in traditional Indian medicine (including Ayurveda) and also in European medicine. The main pharmacological properties of H. indicus include hepatoprotective, anti-cancer, anti-diabetic, antioxidant, neuroprotective, anti-ophidian, cardioprotective, nephroprotective, anti-ulcerogenic, anti-inflammatory, and antimicrobial properties. Phytochemical evaluations of the root have revealed the presence of aromatic aldehydes and their derivatives, phenolics, triterpenoids and many other compounds, some of which were attributed to its bioactivity. This review also compiles a list of Ayurvedic formulations and commercial preparations where H. indicus has been used as an active ingredient. We have included the critical assessment of all the papers cited in this manuscript based on experimental observation and other important points which reflect the loop-holes of research strategy and ambiguity in the papers reviewed in this manuscript. CONCLUSIONS: The study presents an exhaustive and updated review on the traditional, pharmacological and phytochemical aspects of H. indicus with notes on its quality control and toxicological information. Although the crude extracts of H. indicus exhibit an array of pharmacological activities, it is high time to identify more active phyto-constituents by bioactivity-guided isolation besides elucidating their structure-activity relationship. More designed investigations are needed to comprehend the multi-target network pharmacology, to clarify the molecular mode of action and to ascertain the efficacious doses of H. indicus. Moreover, H. indicus is not fully assessed on the basis of its safety and efficacy on human. We hope this review will compile and improve the existing knowledge on the potential utilization of H. indicus in complementary and alternative medicine.