Andrographis paniculata (Burm. f.) Wall. ex Nees: An Updated Review of Phytochemistry, Antimicrobial Pharmacology, and Clinical Safety and Efficacy.
TL;DR: In this article, the authors evaluated the antimicrobial therapeutic potency of A. paniculata and its metabolites, focusing on the mechanism of action in inhibiting invasive microbes and biofilm formation.
Abstract: Infectious disease (ID) is one of the top-most serious threats to human health globally, further aggravated by antimicrobial resistance and lack of novel immunization options. Andrographis paniculata (Burm. f.) Wall. ex Nees and its metabolites have been long used to treat IDs. Andrographolide, derived from A. paniculata, can inhibit invasive microbes virulence factors and regulate the host immunity. Controlled clinical trials revealed that A. paniculata treatment is safe and efficacious for acute respiratory tract infections like common cold and sinusitis. Hence, A. paniculata, mainly andrographolide, could be considered as an excellent candidate for antimicrobial drug development. Considering the importance, medicinal values, and significant role as antimicrobial agents, this study critically evaluated the antimicrobial therapeutic potency of A. paniculata and its metabolites, focusing on the mechanism of action in inhibiting invasive microbes and biofilm formation. A critical evaluation of the secondary metabolites with the aim of identifying pure compounds that possess antimicrobial functions has further added significant values to this study. Notwithstanding that A. paniculata is a promising source of antimicrobial agents and safe treatment for IDs, further empirical research is warranted.
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TL;DR: Wang et al. as discussed by the authors presented a comprehensive review of andrographis paniculata (Burm. f. ex Nees), including its pharmacology, pharmacokinetics, toxicity and pharmaceutical researches.
Abstract: Andrographis paniculata (Burm. f.) Wall. ex Nees, a renowned herb medicine in China, is broadly utilized in traditional Chinese medicine (TCM) for the treatment of cold and fever, sore throat, sore tongue, snake bite with its excellent functions of clearing heat and toxin, cooling blood and detumescence from times immemorial. Modern pharmacological research corroborates that andrographolide, the major ingredient in this traditional herb, is the fundamental material basis for its efficacy. As the main component of Andrographis paniculata (Burm. f.) Wall. ex Nees, andrographolide reveals numerous therapeutic actions, such as antiinflammatory, antioxidant, anticancer, antimicrobial, antihyperglycemic and so on. However, there are scarcely systematic summaries on the specific mechanism of disease treatment and pharmacokinetics. Moreover, it is also found that it possesses easily ignored security issues in clinical application, such as nephrotoxicity and reproductive toxicity. Thereby it should be kept a lookout over in clinical. Besides, the relationship between the efficacy and security issues of andrographolide should be investigated and evaluated scientifically. In this review, special emphasis is given to andrographolide, a multifunctional natural terpenoids, including its pharmacology, pharmacokinetics, toxicity and pharmaceutical researches. A brief overview of its clinical trials is also presented. This review intends to systematically and comprehensively summarize the current researches of andrographolide, which is of great significance for the development of andrographolide clinical products. Noteworthy, those un-cracked issues such as specific pharmacological mechanisms, security issues, as well as the bottleneck in clinical transformation, which detailed exploration and excavation are still not to be ignored before achieving integration into clinical practice. In addition, given that current extensive clinical data do not have sufficient rigor and documented details, more high-quality investigations in this field are needed to validate the efficacy and/or safety of many herbal products.
23 citations
TL;DR: In this article, a questionnaire was designed and validated, which consisted of a total of 51 questions with four sections: demographics (6), knowledge (20), attitude (12), and practice (13) to measure KAP.
Abstract: Misuse and overuse of antibiotics are potential causes of the increasing prevalence of antibiotic resistance (ABR). Having information about the knowledge, attitude, and practices concerning antibiotics use by the public might help control ABR growth. Therefore, this cross-sectional study aimed to investigate the levels and associated factors of knowledge, attitude, and practice (KAP) of antibiotics use among the public. A questionnaire was designed and validated, which consisted of a total of 51 questions with four sections: demographics (6), knowledge (20), attitude (12), and practice (13) to measure KAP. Univariate analysis (using Mann-Whitney U and Kruskal-Wallis analysis) was applied to assess the differences in the mean scores of KAP. Linear regression analysis was performed to identify factors associated with KAP. Finally, using Spearman analysis we have examined the correlation between responses to the KAP. The sample size of this study was 575, with a 99.96% response rate. Regarding knowledge, 73.12% of respondents stated that antibiotics could be used to treat viral infections, and 63.35% of respondents answered that antibiotics could reduce fever. Concerning attitude, 50% of respondents had considered stopping taking antibiotics as soon as symptoms had disappeared. In analyzing practice, we found 40% of respondents obtained antibiotics from a pharmacy without a prescription from a physician, a nurse, or a midwife. Statistical analysis revealed that KAP about antibiotic use was significantly associated with gender, area of residence, level of education, and monthly income (p < 0.05). Our findings concluded that men, respondents with low income, those with low-level education, and those living in rural areas are more prone to excessive use of antibiotics without knowing the adverse effects of improper use and how it can contribute to high ABR. So it is urgently necessary to strengthen policies on antibiotics use, including drug provision, distribution, and sales. In addition, people with low KAP should be a priority consideration in education outreach initiatives.
23 citations
TL;DR: In this paper, a single dose of ethanol (5 g/kg body weight) was intraperitoneally administered after the birth of rat pups on PND-7, which caused oxidative stress accompanied by the activation of phosphorylated-c-Jun N-terminal kinase (p-JNK), nod-like receptor family pyrin domain containing 3 (NLRP3), apoptosis-associated speck-like protein (ASC), and cysteine-aspartic acid protease-1 (caspase-one) proteins to form
Abstract: Neurodegenerative diseases (NDs) extend the global health burden. Consumption of alcohol as well as maternal exposure to ethanol can damage several neuronal functions and cause cognition and behavioral abnormalities. Ethanol induces oxidative stress that is linked to the development of NDs. Treatment options for NDs are yet scarce, and natural product-based treatments could facilitate ND management since plants possess plenty of bioactive metabolites, including flavonoids, which typically demonstrate antioxidant and anti-inflammatory properties. Hypericum oblongifolium is an important traditional medicinal plant used for hepatitis, gastric ulcer, external wounds, and other gastrointestinal disorders. However, it also possesses multiple bioactive compounds and antioxidant properties, but the evaluation of isolated pure compounds for neuroprotective efficacy has not been done yet. Therefore, in the current study, we aim to isolate and characterize the bioactive flavonoid folecitin and evaluate its neuroprotective activity against ethanol-induced oxidative-stress-mediated neurodegeneration in the hippocampus of postnatal day 7 (PND-7) rat pups. A single dose of ethanol (5 g/kg body weight) was intraperitoneally administered after the birth of rat pups on PND-7. This caused oxidative stress accompanied by the activation of phosphorylated-c-Jun N-terminal kinase (p-JNK), nod-like receptor family pyrin domain containing 3 (NLRP3), apoptosis-associated speck-like protein (ASC), and cysteine-aspartic acid protease-1 (caspase-1) proteins to form a complex called the NLRP3-inflammasome, which converts pro-interleukin 1 beta (IL-1B) to activate IL-1B and induce widespread neuroinflammation and neurodegeneration. In contrast, co-administration of folecitin (30 mg/kg body weight) reduced ethanol-induced oxidative stress, inhibited p-JNK, and deactivated the NLRP3-inflammasome complex. Furthermore, folecitin administration reduced neuroinflammatory and neurodegenerative protein markers, including decreased caspase-3, BCL-2-associated X protein (BAX), B cell CLL/lymphoma 2 (BCL-2), and poly (ADP-ribose) polymerase-1 (PARP-1) expression in the immature rat brain. These findings conclude that folecitin is a flavone compound, and it might be a novel, natural and safe agent to curb oxidative stress and its downstream harmful effects, including inflammasome activation, neuroinflammation, and neurodegeneration. Further evaluation in a dose-dependent manner would be worth it in order to find a suitable dose regimen for NDs.
23 citations
TL;DR: Zhang et al. as mentioned in this paper investigated the role of baicalin in T2D-induced hepatocellular cancer, and for the first time, they particularly emphasized the regulation of Baicalin-regulated RNA m6A in hepato-cellular cancers.
19 citations
TL;DR: In this paper, the authors reviewed the current antiviral development based on andrographolide and its derivative compounds, especially on their mechanism of action as antiviral drugs and drug delivery systems.
Abstract: Andrographispaniculata (Burm.f.) Nees has been used as a traditional medicine in Asian countries, especially China, India, Vietnam, Malaysia, and Indonesia. This herbaceous plant extract contains active compounds with multiple biological activities against various diseases, including the flu, colds, fever, diabetes, hypertension, and cancer. Several isolated compounds from A. paniculata, such as andrographolide and its analogs, have attracted much interest for their potential treatment against several virus infections, including SARS-CoV-2. The mechanisms of action in inhibiting viral infections can be categorized into several types, including regulating the viral entry stage, gene replication, and the formation of mature functional proteins. The efficacy of andrographolide as an antiviral candidate was further investigated since the phytoconstituents of A. paniculata exhibit various physicochemical characteristics, including low solubility and low bioavailability. A discussion on the delivery systems of these active compounds could accelerate their development for commercial applications as antiviral drugs. This study critically reviewed the current antiviral development based on andrographolide and its derivative compounds, especially on their mechanism of action as antiviral drugs and drug delivery systems.
13 citations
References
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TL;DR: The optimism of the early period of antimicrobial discovery has been tempered by the emergence of bacterial strains with resistance to these therapeutics, and today, clinically important bacteria are characterized not only by single drug resistance but also by multiple antibiotic resistance.
Abstract: The optimism of the early period of antimicrobial discovery has been tempered by the emergence of bacterial strains with resistance to these therapeutics. Today, clinically important bacteria are characterized not only by single drug resistance but also by multiple antibiotic resistance--the legacy of past decades of antimicrobial use and misuse. Drug resistance presents an ever-increasing global public health threat that involves all major microbial pathogens and antimicrobial drugs.
3,526 citations
TL;DR: A new appreciation of the role of polypharmacology has significant implications for tackling the two major sources of attrition in drug development--efficacy and toxicity.
Abstract: The dominant paradigm in drug discovery is the concept of designing maximally selective ligands to act on individual drug targets. However, many effective drugs act via modulation of multiple proteins rather than single targets. Advances in systems biology are revealing a phenotypic robustness and a network structure that strongly suggests that exquisitely selective compounds, compared with multitarget drugs, may exhibit lower than desired clinical efficacy. This new appreciation of the role of polypharmacology has significant implications for tackling the two major sources of attrition in drug development--efficacy and toxicity. Integrating network biology and polypharmacology holds the promise of expanding the current opportunity space for druggable targets. However, the rational design of polypharmacology faces considerable challenges in the need for new methods to validate target combinations and optimize multiple structure-activity relationships while maintaining drug-like properties. Advances in these areas are creating the foundation of the next paradigm in drug discovery: network pharmacology.
2,915 citations
TL;DR: This review describes and discusses several approaches to selecting higher plants as candidates for drug development with the greatest possibility of success and identifies and discusses advantages and disadvantages of using plants as starting points for drugDevelopment, specifically those used in traditional medicine.
Abstract: In this review we describe and discuss several approaches to selecting higher plants as candidates for drug development with the greatest possibility of success. We emphasize the role of information derived from various systems of traditional medicine (ethnomedicine) and its utility for drug discovery purposes. We have identified 122 compounds of defined structure, obtained from only 94 species of plants, that are used globally as drugs and demonstrate that 80% of these have had an ethnomedical use identical or related to the current use of the active elements of the plant. We identify and discuss advantages and disadvantages of using plants as starting points for drug development, specifically those used in traditional medicine.
1,992 citations
TL;DR: Untapped biological resources, “smart screening” methods, robotic separation with structural analysis, metabolic engineering, and synthetic biology offer exciting technologies for new natural product drug discovery.
Abstract: Historically, the majority of new drugs have been generated from natural products (secondary metabolites) and from compounds derived from natural products. During the past 15 years, pharmaceutical industry research into natural products has declined, in part because of an emphasis on high-throughput screening of synthetic libraries. Currently there is substantial decline in new drug approvals and impending loss of patent protection for important medicines. However, untapped biological resources, "smart screening" methods, robotic separation with structural analysis, metabolic engineering, and synthetic biology offer exciting technologies for new natural product drug discovery. Advances in rapid genetic sequencing, coupled with manipulation of biosynthetic pathways, may provide a vast resource for the future discovery of pharmaceutical agents.
1,683 citations
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TL;DR: A bipartite graph composed of US Food and Drug Administration–approved drugs and proteins linked by drug–target binary associations is built, showing an overabundance of 'follow-on' drugs, that is, drugs that target already targeted proteins.
Abstract: The global set of relationships between protein targets of all drugs and all disease-gene products in the human protein-protein interaction or 'interactome' network remains uncharacterized. We built a bipartite graph composed of US Food and Drug Administration-approved drugs and proteins linked by drug-target binary associations. The resulting network connects most drugs into a highly interlinked giant component, with strong local clustering of drugs of similar types according to Anatomical Therapeutic Chemical classification. Topological analyses of this network quantitatively showed an overabundance of 'follow-on' drugs, that is, drugs that target already targeted proteins. By including drugs currently under investigation, we identified a trend toward more functionally diverse targets improving polypharmacology. To analyze the relationships between drug targets and disease-gene products, we measured the shortest distance between both sets of proteins in current models of the human interactome network. Significant differences in distance were found between etiological and palliative drugs. A recent trend toward more rational drug design was observed.
1,592 citations