ABSTRACT
Molecular pharmacognosy as an emerging interdisciplinary subject based on molecular biology and Chinese materia medica aims to study the synthesis and molecular regulation of secondary metabolites in medicinal plants. Andrographis Herba, the dried aboveground part of Andrographis paniculata, has liver-protecting, bile secretion-promoting, heat-clearing, toxin-removing, antimicrobial, and anti-inflammatory effects. The quality instability caused by plant varieties, environment, and technology in the production of A. paniculata is a limiting factor for the sustainable development of this industry. Based on the research methods of molecular pharmacognosy and omics, the regulation of secondary metabolites of A. paniculata has become the key solution to the quality problems of A. paniculata. This paper summarized the recent research achievements in the molecular pharmacognosy of A. paniculata, including molecular identification of the resources, genetic diversity, multi-omics, biosynthesis of active compounds, and germplasm resource innovation, and prospected the future development trend in this field. In-depth research of molecular pharmacognosy of A. paniculata will provide more scientific and effective technical support for the development of its medicinal value, give new insights into the cultivation of new A. paniculata varieties, and promote the high-quality sustainable development of this industry.
Subject(s)
Pharmacognosy , Andrographis/chemistry , Andrographis/genetics , Drugs, Chinese Herbal/chemistry , Plants, Medicinal/genetics , Plants, Medicinal/chemistry , Andrographis paniculata/genetics , Andrographis paniculata/chemistry , Andrographis paniculata/metabolismABSTRACT
INTRODUCTION: Andrographis paniculata (AP) has been approved by the Thai government for the treatment of mild cases of COVID-19 patients. Increasing use of AP products requires quality control to ensure efficacy and safety. At present, there is no requirement for dissolution test of AP products in the Thai Herbal Pharmacopoeia (THP). OBJECTIVE: This work aimed to examine the contents and dissolution profiles of active diterpenoids, andrographolide (AP1), 14-deoxy-11,12-didehydroandrographolide (AP3), neoandrographolide (AP4), and 14-deoxyandrographolide (AP6) in AP capsules available in Thai markets. MATERIALS AND METHODS: Four extract products (EXT. A-D) and three crude powder products (CRD. A-C) were tested for contents by using HPLC-DAD. Dissolution profiles of four diterpenoids were investigated in different media (pH 1.2, 4.5, 6.8, and 0.01 N HCl + SLS) with apparatus II (paddle type). RESULTS: The AP1 contents were 1.99%-2.90% w/w for crude capsules and 2.84%-16.27% w/w for extract capsules. In the dissolution test, the dissolution percentages of four diterpenoids from crude capsules were higher than those from extract capsules except EXT. A. AP1 in most extract products (EXT. B, C, D) was dissolved in all dissolution media at a lower percentage than the other three diterpenoids. EXT. A (aqueous extract) was the only extract capsule showing the amounts of all diterpenoids dissolved in all media >80% in 45 min. CONCLUSION: The study demonstrated that AP1 content in AP products complied with the acceptance criteria in the THP (80%-120%), and the weight variation also met the United States Pharmacopeia (USP) requirements. However, different dissolution profiles of AP products may lead to different bioavailability of diterpenoids and further affect their efficacy.
Subject(s)
Capsules , Diterpenes , Plant Extracts , Solubility , Diterpenes/chemistry , Diterpenes/analysis , Capsules/chemistry , Plant Extracts/chemistry , Chromatography, High Pressure Liquid/methods , Andrographis/chemistry , Andrographis paniculata/chemistry , Tetrahydronaphthalenes/chemistry , Tetrahydronaphthalenes/analysis , GlucosidesABSTRACT
OBJECTIVE: Nasopharyngeal carcinoma (NPC) remains a challenging cancer to treat. This study investigates the molecular mechanisms of Hedyotis diffusa Willd (HDW) combined with Andrographis paniculata (AP) in treating NPC. METHODS: Key compounds and target genes in HDW and AP were analyzed using network pharmacology. Protein-protein interaction (PPI) networks were constructed with STRING and visualized using Cytoscape. MCODE identified critical clusters, while DAVID facilitated GO and KEGG analyses. In vivo and in vitro experiments evaluated HDW-AP effects on NPC, including tumor volume, weight, Ki-67 expression, cell apoptosis, migration, invasion, cell cycle distribution, and DNA damage. RESULTS: The database identified 495 NPC-related genes and 26 compounds in the HDW-AP pair, targeting 165 genes. Fifty-eight potential therapeutic genes were found, leading to 18 key targets. KEGG analysis revealed a significant impact on 78 pathways, especially cancer pathways. Both in vivo and in vitro tests showed HDW-AP inhibited NPC cell proliferation, migration, invasion, and induced apoptosis. Mechanistically, this was achieved through AKT1 downregulation and VEGFA upregulation. CONCLUSION: The combination of HDW and AP targets 16 key genes to impede the development of NPC, primarily by modulating AKT1 and VEGFA pathways.
Subject(s)
Hedyotis , Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms , Proto-Oncogene Proteins c-akt , Vascular Endothelial Growth Factor A , Proto-Oncogene Proteins c-akt/metabolism , Humans , Vascular Endothelial Growth Factor A/metabolism , Vascular Endothelial Growth Factor A/genetics , Nasopharyngeal Carcinoma/genetics , Nasopharyngeal Carcinoma/pathology , Nasopharyngeal Carcinoma/metabolism , Nasopharyngeal Neoplasms/pathology , Nasopharyngeal Neoplasms/genetics , Nasopharyngeal Neoplasms/metabolism , Animals , Cell Line, Tumor , Mice, Nude , Apoptosis/drug effects , Mice , Gene Expression Regulation, Neoplastic/drug effects , Xenograft Model Antitumor Assays , Andrographis/chemistry , Cell Proliferation/drug effects , Up-Regulation/drug effects , Mice, Inbred BALB C , Cell Movement/drug effects , Drug Synergism , Protein Interaction Maps , Carcinogenesis/drug effects , Andrographis paniculata , Down-Regulation , MaleABSTRACT
Carbon (C) and nitrogen (N) metabolisms participate in N source-regulated secondary metabolism in medicinal plants, but the specific mechanisms involved remain to be investigated. By using nitrate (NN), ammonium (AN), urea (UN), and glycine (GN), respectively, as sole N sources, we found that N sources remarkably affected the contents of diterpenoid lactone components along with C and N metabolisms reprograming in Andrographis paniculata, as compared to NN, the other three N sources raised the levels of 14-deoxyandrographolide, andrographolide, dehydroandrographolide (except UN), and neoandrographolide (except AN) with a prominent accumulation of farnesyl pyrophosphate (FPP). These N sources also raised the photosynthetic rate and the levels of fructose and/or sucrose but reduced the activities of phosphofructokinase (PFK), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), phosphoenolpyruvate carboxylase (PEPC) and pyruvate dehydrogenase (PDH). Conversely, phosphoenolpyruvate carboxykinase (PEPCK) and malate enzyme (ME) activities were upregulated. Simultaneously, citrate, cis-aconitate and isocitrate levels declined, and N assimilation was inhibited. These results indicated that AN, UN and GN reduced the metabolic flow of carbohydrates from glycolysis into the TCA cycle and downstream N assimilation. Furthermore, they enhanced arginine and GABA metabolism, which increased C replenishment of the TCA cycle, and increased ethylene and salicylic acid (SA) levels. Thus, we proposed that the N sources reprogrammed C and N metabolism, attenuating the competition of N assimilation for C, and promoting the synthesis and accumulation of andrographolide through plant hormone signaling. To obtain a higher production of andrographolide in A. paniculata, AN fertilizer is recommended in its N management.
Subject(s)
Andrographis paniculata , Diterpenes , Plant Extracts , Carbon , SeedlingsABSTRACT
Andrographis paniculata is an important medicinal plant in the Lingnan region of China, which has the functions of clearing heat, removing toxins, and resisting bacteria and inflammation. The TCP gene family is a class of transcription factors that regulate plant growth, development, and stress response. In order to analysis the role of the TCP gene family under abiotic stress in A. paniculata, this study identified the TCP gene family of A. paniculata at the genome-wide level and analyzed its expression pattern in response to abiotic stress. The results showed that the A. paniculata TCP gene family had 23 members, with length of amino acid ranging from 136 to 508, the relative molecular mass between 14 854.71 and 55 944.90 kDa, and the isoelectric point between 5.67 and 10.39. All members were located in the nucleus and unevenly distributed on 13 chromosomes. Phylogenetic analysis classified them into three subfamilies: PCF, CIN and CYC/TB1. Gene structure and conserved motif analysis showed that most members of the TCP gene family contained motif 1, motif 2, motif 3 in the same order and 1-3 CDS. The analysis of promoter cis-acting elements showed that the transcriptional expression of the TCP gene family in A. paniculata might be induced by light, hormones, and adversity stress. In light of the expression pattern analysis and qRT-PCR verification, the expression of ApTCP4, ApTCP5, ApTCP6, and ApTCP11 involved in response by various abiotic stresses such as drought, high temperature, and MeJA. This study lays the foundation for in-depth exploration of the functions of A. paniculata TCP genes in response to abiotic stress.
Subject(s)
Amino Acids , Andrographis paniculata , Phylogeny , China , Droughts , Gene Expression Regulation, Plant , Plant Proteins/geneticsABSTRACT
CONTEXT: The therapeutic potential of andrographolide is hindered by its poor oral bioavailability and unpredictable pharmacokinetics, primarily due to its limited water solubility. OBJECTIVE: This work aimed to enhance the solubility and pharmacokinetics of andrographolide, a bioactive compound in Andrographis paniculata (Burm. f.) Nees (Acanthaceae), using solubilizing agents and a bioenhancer. MATERIALS AND METHODS: Four groups of beagles were compared: (1) A. paniculata powder alone (control), (2) A. paniculata powder with 50% weight/weight (w/w) ß-cyclodextrin solubilizer, (3) A. paniculata powder with 1% w/w sodium dodecyl sulfate (SDS) solubilizer, and (4) A. paniculata powder co-administered with 1% w/w SDS solubilizer and 10% piperine bioenhancer. All groups received a consistent oral dose of 3 mg/kg of andrographolide, administered both as a single dose and multiple doses over seven consecutive days. RESULTS: Thirteen chemical compounds were identified in A. paniculata powder, including 7 diterpenoids, 5 flavonoids, and 1 phenolic compound. A. paniculata co-administration with either 50% w/w ß-cyclodextrin or 1% w/w SDS, alone or in combination with 10% w/w piperine, significantly increased systemic andrographolide exposure by enhancing bioavailability (131.01% to 196.05%) following single and multiple oral co-administration. Glucuronidation is one possible biotransformation pathway for andrographolide, as evidenced by the excretion of glucuronide conjugates in urine and feces. CONCLUSION: The combination of solubilizing agents and a bioenhancer improved the oral bioavailability and pharmacokinetics of andrographolide, indicating potential implications for A. paniculata formulations and clinical therapeutic benefits. Further investigation in clinical studies is warranted.
Subject(s)
Alkaloids , Andrographis , Benzodioxoles , Diterpenes , Piperidines , Polyunsaturated Alkamides , beta-Cyclodextrins , Animals , Dogs , Andrographis paniculata , Biological Availability , Bioenhancers , Powders , Andrographis/chemistry , Plant Extracts , ExcipientsABSTRACT
Kalmegh (Andrographis paniculata) spatiotemporally produces medicinally-important ent-labdane-related diterpenoids (ent-LRDs); andrographolide (AD), 14-deoxy-11,12-didehydroandrographolide (DDAD), neoandrographolide (NAD). ApCPS1 and ApCPS2, the ent-copalyl pyrophosphate (ent-CPP)-producing class II diterpene synthases (diTPSs) were identified, but their contributions to ent-CPP precursor supply for ent-LRD biosynthesis were not well understood. Here, we characterized ApCPS4, an additional ent-CPP-forming diTPS. Further, we elucidated in planta function of the ent-CPP-producing diTPSs (ApCPS1,2,4) by integrating transcript-metabolite co-profiles, biochemical analysis and gene functional characterization. ApCPS1,2,4 localized to the plastids, where diterpenoid biosynthesis occurs in plants, but ApCPS1,2,4 transcript expression patterns and ent-LRD contents revealed a strong correlation of ApCPS2 expression and ent-LRD accumulation in kalmegh. ApCPS1,2,4 upstream sequences differentially activated ß-glucuronidase (GUS) in Arabidopsis and transiently-transformed kalmegh. Similar to higher expression of ApCPS1 in kalmegh stem, ApCPS1 upstream sequence activated GUS in stem/hypocotyl of Arabidopsis and kalmegh. However, ApCPS2,4 upstream sequences weakly activated GUS expression in Arabidopsis, which was not well correlated with ApCPS2,4 transcript expression in kalmegh tissues. Whereas, ApCPS2,4 upstream sequences could activate GUS expression at a considerable level in kalmegh leaf and roots/calyx, respectively, suggesting the involvement of transcriptional regulator(s) of ApCPS2,4 that might participate in kalmegh-specific diterpenoid pathway. Interestingly, ApCPS2-silenced kalmegh showed a drastic reduction in AD, DDAD and NAD contents and compromised defense against insect herbivore Spodoptera litura. However, ent-LRD contents and herbivore defense in ApCPS1 or ApCPS4-silenced plants remained largely unaltered. Overall, these results suggested an important role of ApCPS2 in producing ent-CPP for medicinal ent-LRD biosynthesis and defense against insect herbivore.
Subject(s)
Alkyl and Aryl Transferases , Andrographis , Arabidopsis , Diterpenes , Glucosides , Tetrahydronaphthalenes , Andrographis paniculata , Arabidopsis/metabolism , Herbivory , NAD/metabolism , Alkyl and Aryl Transferases/metabolism , Diterpenes/metabolism , Andrographis/genetics , Andrographis/metabolismABSTRACT
The plant Andrographis paniculata has a long history of cultivation in Southeast Asia, especially its extensive anti-inflammatory activity, and the famous natural antibiotic andrographolide comes from this plant. In China, A. paniculata, as the main crop, has become a major source of traditional Chinese medicine (TCM) for the clinical treatment of inflammation. To further explore the diverse diterpene lactones with better anti-inflammatory activity from A. paniculata, twenty-one ent-labdanes, including six undescribed compounds (andropanilides D-I), were isolated. Their structures with absolute configurations were thoroughly determined by comprehensive NMR spectroscopic data, HRESIMS analysis and quantum chemical calculations. All isolated compounds were evaluated for anti-inflammatory activities based on the Griess method. Meanwhile, after structure-activity relationships analysis, the anti-inflammatory activity of andropanilide D (1) (IC50 = 2.31 µM) was found to be better than that of the positive control drug (dexamethasone, IC50 = 6.52 µM) and andrographolide (IC50 = 5.89 µM). Further mechanisms of activity indicated that andropanilide D significantly reduced the secretion of TNF-α, IL-6 and IL-1ß and downregulated the protein expression of COX-2 and iNOS in LPS-induced RAW264.7 macrophages in a concentration-dependent manner based on Western blot and ELISA experiments. In conclusion, andropanilide D possesses potential medicinal value for the treatment of inflammation and further expands the material basis of the anti-inflammatory effect of A. paniculata.
Subject(s)
Andrographis , Diterpenes , Andrographis paniculata , Andrographis/chemistry , Andrographis/metabolism , Anti-Inflammatory Agents/pharmacology , Plant Extracts/pharmacology , Diterpenes/chemistry , InflammationABSTRACT
Cancer is one of the deadliest illnesses of the 21st century. Chemotherapy and radiation therapies both have considerable side effects. Antitumor antibiotics are one of them. Coughs, common colds, fevers, laryngitis, and infectious disorders have all been treated with Andrographis paniculata for centuries. Extracts of Andrographis effectively treat various ailments, as well as cancer. The most active molecule in Andrographis paniculata is andrographolide a, diterpene, and lactone. Andrographis paniculata and its derivatives have long been used to treat various ailments. Anti-inflammatory and cancerfighting characteristics have been observed in Andrographolide. Andrographolide, a diterpene lactone separated from Andrographis paniculata, has also been shown to have important criticalessential biological protective properties. It has also been suggested that it could be used to treat major human diseases like-rheumatoid like rheumatoid, colitis, and Parkinsons disease. This summary aims to highlight Andrographolide as a promising cancer treatment option. Several databases were searched for andrographolides cytotoxic/anti-cancer effects in pre-clinical and clinical research to serve this purpose. Several studies have shown that Andrographolide is helpful in cancer medication, as detailed in this review.
Subject(s)
Andrographis , Diterpenes , Neoplasms , Humans , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Andrographis paniculata , Nanoparticle Drug Delivery System , Neoplasms/drug therapy , Diterpenes/pharmacology , Diterpenes/therapeutic use , LactonesABSTRACT
Andrographispaniculata (kalmegh) is also known as "king of bitters", is an herbaceous plant belongs to family Acanthaceae. The therapeutic effect is due to presence of diterpenoid lactone derivatives of A. paniculata mainly andrographolide. The main purpose of this review includes detailed (past and present) study of A. paniculata and its most important component andrographolide a diterpenoid lactone with respect to its botany, phytochemistry, molecular docking analysis and pharmacological effects i.e., therapeutic benefits. In reference to the search, we also compiled variety of dosage forms available, which are made up of A. paniculata extract and Andrographolide such as tablets and capsules. This review also discusses reported methods of extraction of phytoconstituents, pharmacokinetics of main components, their molecular docking analysis data and main therapeutic applications with their proposed mechanism of actions in various diseases. According to data collected, A. paniculata is becoming more and more valuable as a therapeutic herb.
Subject(s)
Andrographis , Botany , Diterpenes , Andrographis paniculata , Molecular Docking Simulation , Andrographis/chemistry , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Plant Extracts/chemistry , Diterpenes/pharmacology , Diterpenes/therapeutic use , Diterpenes/analysis , LactonesABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: The King of Bitters (Andrographis paniculata) is a plant used to cure a wide range of infectious diseases which includes malaria, fever and others. However, there is a paucity of scientific evidence of its effect on male reproductive indices during malaria treatment. AIM OF THE STUDY: The aim of this study is to evaluate the effect of supplemented diet on antiplasmodial, hematological and male reproductive indices in mice infected with Plasmodium berghei. MATERIALS AND METHODS: Aqueous extract of A. paniculata (King of Bitters, KGB) was prepared and the total phenol and flavonoid contents were determined. Forty-two mice, weighing 20-25 g, were distributed into 7 groups consisting of 6 mice each. The mice were innoculated with strain NK65 Plasmodium berghei (Chloroquine, CQ sensitive) and the parasitemia suppression was assessed. The mice were fed with the dietary supplementation of KGB at varying inclusions (2.5%, 5%, 7.5%, and 10%) and administered 10 mg/kg CQ (which served as the positive control) for 5 consecutive days after infection was established. The reactive malondialdeahyde (MDA), antioxidant [superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH)] and the hematological (hemoglobin, packed cell volume and red blood cell) parameters in the infected mice were determined. The reproductive indices (serum testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), sperm count, sperm motility, and sperm viability) and testis histopathology were also assessed. RESULT: The result revealed that KGB had a total phenol content of 32.55 mgGAE/g and total flavonoid content of 19.71 mgQUE/g. The infected mice treated with the dietary supplementation of KGB showed significantly decreased (p < 0.05) parasitaemia and MDA levels. Furthermore, the 7.5% dietary inclusion showed significant improvement in the antioxidant, hematological and reproductive indices as well as the restoration of testis morphology as seen in the histopathology plate of the infected mice treated with KGB. Hence, this study suggests that the KGB- supplemented diet (7.5%) may be a potential alternative and complementary therapy in the treatment of malaria infection and reproductive disorders.
Subject(s)
Antimalarials , Malaria , Male , Animals , Mice , Antimalarials/pharmacology , Antimalarials/therapeutic use , Antioxidants/pharmacology , Antioxidants/therapeutic use , Plasmodium berghei , Andrographis paniculata , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Sperm Motility , Seeds , Malaria/drug therapy , Dietary Supplements , Diet , Flavonoids/pharmacology , Phenols/pharmacologyABSTRACT
The present investigation looked into the various biomedical potentials of Andrographis paniculata shoot extracts. The results showed that the methanol extract (Met-E) of A. paniculata contains more phytochemicals than the acetone and petroleum ether extracts, including alkaloids, saponins, tannins, phenolics, flavonoids, glycosides, terpenoids, phytosterol, steroids, and protein. Accordingly, the Met-E alone showed considerable bactericidal activity (through agar well diffusion method) against the bacterial pathogens namely Shigella dysenteriae, Bacillus cereus, Salmonella typhi, Enterococcus faecalis, Pseudomonas aeruginosa, Klebsiella pneumoniae, Staphlococcus aureus, E. coli, and B. subtilis. This bactericidal activity was found as dose dependent manner, since at 1000 µg ml concentration, the Met-E showed better antibacterial activity. Similarly, at increased concentration (1000 µg ml) it showed notable antidiabetic (α-amylase inhibition: 74.31% and α-glucosidase inhibition: 72.34%), antioxidant (DPPH: 78.24%), and anti-inflammatory (albumin denaturation inhibition: 79.84% and lipoxigenase inhibition: 69.4%) activities. The phytochemical profiling of Met-E was characterized by UV-visible spectrophotometer (UV-vis), Gas Chromatography-Mass Spectrometry (GC/MS), Fourier transform infrared (FTIR), and High Performance Liquid Chromatography (HPLC) analyses. The results showed the Met-E contain bioactive compounds such as gallic acid, epicatechin, catechin, naringin, vitexin-2-rhamnoside, taxifolin, kaempferol, hesperidin, myricetin, rutin, quercetin, phloretin, and ursolic acid compounds. While most of these substances have been recognised for their pharmacological application perspective, the biological properties of particular substances must be studied in the future using in-vivo strategies.
Subject(s)
Alkaloids , Andrographis paniculata , Escherichia coli , Plant Leaves , Plant Extracts/pharmacology , Plant Extracts/chemistry , Anti-Bacterial Agents/chemistry , Alkaloids/analysis , Phytochemicals/pharmacology , Phytochemicals/analysis , Phytochemicals/chemistry , Antioxidants/pharmacology , Antioxidants/analysisABSTRACT
An in-vitro investigation was performed to evaluate and compare the phytochemical, antioxidant, antidiabetic, anti-inflammatory, and anti-lung cancer activities of methanol extracts of aerial parts of Andrographis paniculata and Trianthema portulacastrum. Furthermore studied major functional groups of phytochemicals present in the methanol extracts of these plants through Fourier transform infrared (FTIR) analysis. The results showed that the methanol extract of A. paniculata contain more number of pharmaceutically valuable phytochemicals such as alkaloids, flavonoids, terpenoids, saponin, glycoside, phytosterol, and tannin than T. portulacastrum. Similar way the methanol extract of A. paniculata showed considerable dose dependent antioxidant (DPPH: 63%), antidiabetic (α-amylase: 82.31% and α-glucosidase inhibitions: 72.34%), and anti-inflammatory (albumin-denaturation inhibition: 76.3% and anti-lipoxygenase: 61.2%) activities (at 900 µg mL-1 concentration) than T. portulacastrum. However, the anti-lung cancer activities of these test plants against A549 cells were not considerable. According to FTIR analysis, the A. paniculata methanol extract has a larger number of characteristic peaks attributed to the active functional groups of pharmaceutically valuable bioactive components that belong to different types of phytochemicals. These findings imply that A. paniculata methanol extracts can be used for additional research, such as bioactive compound screening and purification, as well as assessing their potential biomedical uses in various in-vitro and in-research settings.
Subject(s)
Andrographis , Neoplasms , Humans , Hypoglycemic Agents/pharmacology , Andrographis paniculata , Methanol/chemistry , Antioxidants/pharmacology , Andrographis/chemistry , Anti-Inflammatory Agents/pharmacology , Plant Extracts/pharmacology , Plant Extracts/chemistryABSTRACT
The Andrographis paniculata recognized as most valuable medicinal plant in folk medicine. Hence, this research was designed to evaluate antibacterial potential of petroleum ether (PE) and methanol (ME) extracts of A. paniculata against skin infection causing bacterial pathogens such as Staphylococcus aureus, Streptococcus pyogenes, Klebsiella pneumoniae, Enterobacter aerogenes, Proteus vulgaris, and Propionibacterium acnes. Also assessed the antidiabetic (α-glucosidase and α-amylase inhibition assay), antioxidant, and photoprotective potential of PE and ME extract analyses. The major bioactive compounds were identified and characterized through UV, FTIR, 1H-NMR and 13C-NMR spectra analyses. The ME extract contain more number of phytochemicals (alkaloids, flavonoids, saponins, terpenoids, glycoside, protein, and phytosterol) than PE extract. The antibacterial activity result also revealed that the ME (as dose dependent) extract showed better activity at 250 mg mL-1 as in the following order: P. acnes (6-29 mm) > K. pneumoniae (3-28 mm) > S. aureus (3-27 mm) > P. vulgaris (3-26 mm) > S. pyogenes (2-25 mm) > E. aerogenes (1-23 mm). PE: E. aerogenes (3-20 mm) > P. vulgaris (2-19 mm) > P. acnes (3-18 mm) > K. pneumoniae (3-17 mm) > S. aureus (2-16 mm) > S. pyogenes (0-11 mm). The MIC value of ME extract was found as 100-150 mg mL-1 and it was better than PE extract. Similarly, the ME also possesses dose based α-glucosidase inhibition activity as up to 85% at 250 mg mL-1 concentration. The fluorescence spectra analysis method also stated that the ME extract possess photoprotective bioactive agent. The ME fractions (F01 and F02) obtained from TLC and column chromatogram were identified as 3-O-ß-d-glucosyl-14- deoxyandrographiside and 14-deoxyandrographolide respectively through UV, FTIR, 1H-NMR and 13C-NMR spectra analyses. Such compounds may be responsible for significant antibacterial activity against pathogenic bacteria causing skin infections, excellent antidiabetic activity, as well as photoprotective potential.
Subject(s)
Andrographis paniculata , Plant Extracts , Plant Extracts/pharmacology , Plant Extracts/chemistry , Staphylococcus aureus , alpha-Glucosidases , Anti-Bacterial Agents/pharmacology , Hypoglycemic Agents/pharmacology , Solvents , MethanolABSTRACT
The quality standards for Andrographis paniculata, a widely used medicinal herb, exhibited significant variations across different pharmacopeias. In this study, we compared the HPLC content determination methods and total lactone content of A. paniculata samples from different regions, as specified in the Chinese (CP), United States (USP), European (EP), Thai (TP), and Indian pharmacopeias (IP), as well as the Hong Kong Chinese Materia Medica Standards (HK). We aimed to assess the differences and similarities among these pharmacopeias and harmonized international quality standards for A. paniculata. The analysis revealed variations in sample preparation, liquid chromatographic conditions, fingerprint profiles, and total lactone content among the different pharmacopeias. Specifically, the CP and HK methods exhibited superior sample preparation and chromatographic separation. Further comparing the content of 20 A. paniculata samples with the CP, USP, EP and HK methods showed consistent determinations for the same components, indicating similar detection capabilities. The discrepancies in total lactone content primarily stemmed from differences in the number and types of detected compounds. Moreover, the acceptance criteria exhibited a stringency in the order CP > HK > EP > USP. In conclusion, this comparison analysis of content determination in CP, USP, HK, EP, TP and IP provided a scientific foundation for the international standardization and trade regulations of A. paniculata. It also served as a valuable reference for the development of international quality standards for other medicinal herbs, facilitating the harmonization of global pharmaceutical standards.
Subject(s)
Andrographis , Diterpenes , Plants, Medicinal , Andrographis paniculata , Andrographis/chemistry , Diterpenes/analysis , Plants, Medicinal/chemistry , Lactones , Reference Standards , Plant Extracts/chemistryABSTRACT
BACKGROUND: Alzheimer's disease (AD) is the most prevalent neurodegenerative and remains incurable. Aluminum is a potent neurotoxin associated with AD. The main pathological features of AD are extracellular amyloid-ß protein deposition and intracellular hyperphosphorylated Tau protein. A body of evidence suggest that oxidative stress and autophagy are involved in the pathogenesis of AD. Andrographis paniculata (AP) is a native plant with anti-inflammatory, anti-oxidative stress, and regulation of autophagy properties. AP significantly alleviated cognitive impairments, reduced Aß deposition and has neuroprotective effect. However, its effects on aluminum-induced AD model have not been studied much. In this study, we investigated whether AP protect against aluminum-induced neurotoxicity through regulation of p62-Kelch-like ECH-associated protein 1(Keap1)-Nuclear factor E2 related factor 2 (Nrf2) pathway and activation autophagy in vivo and in vitro. METHODS: UPLC-ESI-qTOF-MS/MS was used to identify the chemical constituents of AP ethanol extract. The mice with cognitive deficit were established by injecting aluminum chloride and D-galactose, and treated with either AP extract (200, 400, or 600 mg/kg/d) or andrographolide (2 mg/kg/2d).The spatial memory ability was detected by Morris water maze, HE staining were used to detect in brain tissue,Oxidative stress indexs and SOD activity in both serum and brain tissue were detected by kit.The expression of p62-Nrf2 pathway proteins were measured via western blotting. Furthermore, the neurotoxicity model was induced by aluminum maltolate (700 µM) in PC12 cells. Following AP and andrographolide treatment, the cell viability was detected. The relevant mRNA and protein expressions were detected in cells transfected with the p62 siRNA. RESULTS: The main active components of AP included andrographolide, neoandrographolide and deoxyandrographolide as identified. AP and andrographolide significantly improved the spatial memory ability of mice, attenuated pathological changes of hippocampal cells, reduced the level of malondialdehyde, and increased superoxide dismutase activity in serum or brain tissue as compared to model control. In addition, the Nrf2, p62 and LC3B-II proteins expression were increased, and p-Tau and Keap1 proteins were decreased in the hippocampus after AP and andrographolide treatment.Furthermore, AP increased aluminum maltolate-induced cell viability in PC12 cells. Silencing p62 could reverse the upregulation expression of Nrf2 and downregulation of Keap1 and Tau proteins induced by AP in aluminum maltolate-treated cells. CONCLUSIONS: AP had neuroprotective effects against aluminum -induced cognitive dysfunction or cytotoxicity, which was involved in the activation of the p62-keap1-Nrf2 pathway and may develop as therapeutic drugs for the treatment of AD. However, this study has certain limitations, further optimize the protocol or model and study the molecular mechanism of AP improving AD.
Subject(s)
Alzheimer Disease , Cognitive Dysfunction , Neuroprotective Agents , Signal Transduction , Animals , Mice , Rats , Aluminum/toxicity , Andrographis paniculata/chemistry , Cognitive Dysfunction/chemically induced , Cognitive Dysfunction/drug therapy , Ethanol , Kelch-Like ECH-Associated Protein 1/metabolism , Neuroprotective Agents/pharmacology , NF-E2-Related Factor 2/metabolism , Tandem Mass Spectrometry , Signal Transduction/drug effects , Plant Extracts/chemistryABSTRACT
The medical plant research has received more attention among researchers especially after the Covid-19 pandemic. This research performed to evaluate the antifungal, anti-lung cancer (A549), and anti-hyperglycemic activities of aqueous extract of Andrographis paniculata flower. Interestingly, A. paniculata flower aqueous extract contains pharmaceutically valuable phytochemicals such as alkaloid, phenolics, terpenoids, tannins, flavonoids, and protein. It also showed fine antifungal activity against test fungal pathogens in the following order as: Aspergillus niger > Fusarium solani > Trichoderma harzianum > A. parasiticus > P. expansum > Penicillium janthinellum with lowest MIC values as ranged from 100 to 300 µg mL-1. Interestingly, this aqueous extract also showed considerable anti-lung cancer activity, evidenced by dose and time dependent lung cancer cell line (A549) growth/proliferation inhibition/cytotoxicity activity (65%) at 300 µg mL-1 concentration. This can be achieved by plant extract through inducing the secretion of apoptosis related proteins such as TNF α, IFN-γ, and interleukin 2 leads to apoptosis in A549 cells. It also showed fine anti-diabetic activity by inhibiting α -amylase (58.41%) than α-glucosidase (54.74%) at 200 µg mL-1 concentration. The UV as well as FTIR results demonstrated that the aqueous extract of A. paniculata flower contains pharmaceutically valuable bioactive compounds, which may be responsible for the wide range of biomedical applications.
Subject(s)
Andrographis , Antifungal Agents , Humans , Antifungal Agents/chemistry , Antifungal Agents/pharmacology , Andrographis paniculata , Pandemics , Andrographis/chemistry , Flowers , Water , Hypoglycemic Agents/pharmacologyABSTRACT
Acute viral pharyngitis is a self-limited disease but the symptoms, a sore throat in particular, can affect one's quality of life. Medicine for symptom relief is the main treatment. Recently, many studies have shown that Andrographis paniculata was efficacious in treating many diseases, including upper respiratory infections. However, adverse reactions to systemic intake are a concern. Therefore, A. paniculata spray is intended to reduce systemic adverse reactions and provide patients with more comfort as its local use. This randomized, double-blind study enrolled 60 adult patients with acute viral pharyngitis. All patients were asked to score the severity of symptoms including a sore throat, difficulty swallowing, and coughing using an 11-point numeric rating scale from 0 to 10. A physical examination was performed to score the severity of erythematous and swollen mucosa using a 0-3 score (0 = no, 1 = mild, 2 = moderate, and 3 = severe). The patients were randomized to receive treatment with either an A. paniculata spray or a positive control chamomile spray. Results revealed a significant reduction in the severity of all signs and symptoms in both groups (p < 0.05). The duration of treatment response in the A. paniculata spray group was 1.9 ± 0.7 days compared to 2.5 ± 1.2 days in the chamomile spray group (p = 0.049). No adverse events were noted in either group. A. paniculata spray is safe and highly efficacious in treating acute viral pharyngitis and can reduce symptoms more rapidly than a positive control spray.
Subject(s)
Andrographis paniculata , Pharyngitis , Adult , Humans , Quality of Life , Pharyngitis/drug therapy , Cough , PainABSTRACT
Neurodegenerative diseases (NDs) affect millions of people worldwide, and to date, Alzheimer's and Parkinson's diseases are the most common NDs. Of the many risk factors for neurodegeneration, the aging process has the most significant impact, to the extent that it is tempting to consider neurodegenerative disease as a manifestation of accelerated aging. However, genetic and environmental factors determine the course of neurodegenerative disease progression. It has been proposed that environmental stimuli influence neuroplasticity. Some clinical studies have shown that healthy lifestyles and the administration of nutraceuticals containing bioactive molecules possessing antioxidant and anti-inflammatory properties have a preventive impact or mitigate symptoms in previously diagnosed patients. Despite ongoing research efforts, the therapies currently used for the treatment of NDs provide only marginal therapeutic benefits; therefore, the focus is now directly on the search for natural products that could be valuable tools in combating these diseases, including the natural compound Andrographis paniculata (Ap) and its main constituent, andrographolide (Andro). Preclinical studies have shown that the aqueous extract of Ap can modulate neuroinflammatory and neurodegenerative responses, reducing inflammatory markers and oxidative stress in various NDs. Therefore, in this review, we will focus on the molecular mechanisms by which Ap and Andro can modulate the processes of neurodegeneration and neuroinflammation, which are significant causes of neuronal death and cognitive decline.
Subject(s)
Andrographis , Neurodegenerative Diseases , Humans , Andrographis paniculata , Neuroinflammatory Diseases , Neurodegenerative Diseases/drug therapy , Plant Extracts/pharmacology , Plant Extracts/therapeutic useABSTRACT
Recent studies have highlighted the necessity to thoroughly evaluate medicinal plants due to their therapeutic potential. The current study delves into the phytochemical profile, antioxidant capacity, and hepatoprotective effect of Andrographis paniculata. The investigation specifically targets its effectiveness in mitigating liver dysfunction induced by carbon tetrachloride (CCl4) in Wistar albino rats, aiming to uncover its promising role as a natural remedy for liver-related ailments. A. paniculata leaf extract was screened for phytoconstituents and antioxidant and hepatoprotective effects in Wistar albino rats against CCl4-induced liver dysfunction. Phytochemical analysis revealed the presence of flavonoids, alkaloids, and phenolic compounds in all extracts. The phenolic concentration ranged from 10.23 to 19.52 mg gallic acid per gram of the sample, while the highest flavonoid concentration was found in the ethanol fraction (8.27 mg rutin equivalents per gram). The antioxidant activity varied from 10.23 to 62.23. GC-MS analysis identified several phytochemicals including octadecanoic acid, stigmasterol, phenanthrenecarboxylic acid, and others. Effects of the ethanol extract of A. paniculata were evaluated in four groups of animals. Biochemical estimations of serum glutamine oxaloacetate transaminase, serum glutamine pyruvate transaminase, and serum bilirubin were significantly higher (p < 0.05) in the CCl4-treated group. Treatment with 300 mg/kg b.w. of the ethanol extract of A. paniculata significantly (p < 0.05) decreased these serum enzymes. Lipid peroxidation levels in carbon tetrachloride-treated animals showed a substantial (p < 0.05) rise when compared to untreated animals, while the lipid peroxidation levels were considerably (p < 0.05) reduced after treatment with ethanol extract at 300 mg/kg b.w. Liver biochemical catalase activities were significantly reduced in the carbon tetrachloride-treated animals. The results of this study conclusively demonstrate that A. paniculata extracts are a rich source of phytochemicals and possess significant antioxidant, free radical scavenging, and hepatoprotective properties.