In-silico study unveils potential phytocompounds in Andrographis paniculata against E6 protein of the high-risk HPV-16 subtype for cervical cancer therapy.

Despite therapeutic advancements, cervical cancer caused by high-risk subtypes of the human papillomavirus (HPV) remains a leading cause of cancer-related deaths among women worldwide. This study aimed to discover potential drug candidates from the Asian medicinal plant Andrographis paniculata, demonstrating efficacy against the E6 protein of high-risk HPV-16 subtype through an in-silico computational approach. The 3D structures of 32 compounds (selected from 42) derived from A. paniculata, exhibiting higher binding affinity, were obtained from the PubChem database. These structures underwent subsequent analysis and screening based on criteria including binding energy, molecular docking, drug likeness and toxicity prediction using computational techniques. Considering the spectrometry, pharmacokinetic properties, docking results, drug likeliness, and toxicological effects, five compounds-stigmasterol, 1H-Indole-3-carboxylic acid, 5-methoxy-, methyl ester (AP7), andrographolide, apigenin and wogonin-were selected as the potential inhibitors against the E6 protein of HPV-16. We also performed 200 ns molecular dynamics simulations of the compounds to analyze their stability and interactions as protein-ligand complexes using imiquimod (CID-57469) as a control. Screened compounds showed favorable characteristics, including stable root mean square deviation values, minimal root mean square fluctuations and consistent radius of gyration values. Intermolecular interactions, such as hydrogen bonds and hydrophobic contacts, were sustained throughout the simulations. The compounds displayed potential affinity, as indicated by negative binding free energy values. Overall, findings of this study suggest that the selected compounds have the potential to act as inhibitors against the E6 protein of HPV-16, offering promising prospects for the treatment and management of CC.

A Diterpenoid of the Medicinal Plant Andrographis paniculata Targets Cutaneous TRPV3 Channel and Relieves Itch.

Transient receptor potential vanilloid subtype 3 (TRPV3) is an ion channel implicated in skin physiology and itch. TRPV3 inhibitors can present a novel strategy for combating debilitating itch conditions, and medicinal plants are a natural pool of such compounds. Here, we report the isolation of a TRPV3-inhibiting compound from Andrographis paniculata, a medicinal plant with anti-inflammatory properties whose bioactive components are poorly characterized in terms of molecular targets. Using 1H and 13C NMR and high-resolution mass spectrometry, the compound was identified as a labdane-type diterpenoid, 14-deoxy-11,12-didehydroandrographolide (ddA). The activity of the compound was evaluated by fluorescent calcium assay and manual whole-cell patch-clamp technique. ddA inhibited human TRPV3 in stably expressing CHO and HaCaT keratinocytes, acting selectively among other TRP channels implicated in itch and inflammation and not showing toxicity to HaCaT cells. Antipruritic effects of the compound were evaluated in scratching behavior models on ICR mice. ddA suppressed itch induced by the TRPV3 activator carvacrol. Additionally, ddA potently suppressed histamine-induced itch with efficacy comparable to loratadine, a clinically used antihistamine drug. These results suggest the potential of ddA as a possible safe and efficacious alternative for antipruritic therapy.

[Research progress in molecular pharmacognosy of Andrographis paniculata].

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.

Tissue-Level Effect of Andrographis and Ashwagandha Metabolites on Metabolic and Inflammatory Gene Expression in Skeletal Muscle and Adipose Tissue: An Ex Vivo/In Vitro Investigation.

Adipose tissue and skeletal muscle dysfunction play a central role in cardiometabolic morbidity. Ashwagandha and Andrographis are purported to have anti-inflammatory and antioxidant activity, but this is based on exposure of cells to the parent compounds ignoring phytochemical absorption and metabolism. We explored the anti-inflammatory/antioxidant effects of ashwagandha and Andrographis in ex vivo human models of skeletal muscle and adipose tissue. Healthy participants supplemented with 2000 mg/day Andrographis (n = 10) or 1100 mg/day ashwagandha (n = 10) for 28 days. Sera collected pre (D0) and post (D28) supplementation were pooled by timepoint and added to adipose explant (AT) and primary human myotube (SKMC) culture media (15% v/v) for treatment. A Taqman panel of 56 genes was used to quantify these. In AT, treatment with ashwagandha sera decreased the expression of genes involved in antioxidant defence and inflammatory response (CCL5, CD36, IL6, IL10, ADIPOQ, NFEL2, UCP2, GPX3, GPX4; geometric 95% CI for fold change > 1) and altered the expression of genes involved in fatty acid metabolism. In SKMC, ashwagandha sera altered FOXO1 and SREBF1 expression. Andrographis sera decreased IL18 and SERPINEA3 expression in AT. This physiologically relevant in vitro screening characterises the effects of ashwagandha in AT to guide future clinical trials.

Synthetic Modifications of Andrographolide Targeting New Potential Anticancer Drug Candidates: A Comprehensive Overview.

This review collects the synthetic modifications performed on andrographolide, a natural molecule derived from Andrographis paniculata, for oncology applications. Various pharmacomodulations were carried out, and the products were tested on different cancer cell lines. The impact of these modifications was analyzed with the aim of mapping the positions essential for activity to facilitate future research in this field. However, this study makes it clear that, in addition to structural modifications of the molecule, which can result in varying degrees of effectiveness in targeting interactions, the lipophilic capacity of the structures obtained through hemisynthesis is of significant importance.

Comparison of diterpenoid contents and dissolution profiles of selected Andrographis paniculata crude and extract capsules.

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.

Herbal Medicines for the Treatment of Active Ulcerative Colitis: A Systematic Review and Meta-Analysis.

Herbal medicines are used by patients with IBD despite limited evidence. We present a systematic review and meta-analysis of randomized controlled trials (RCTs) investigating treatment with herbal medicines in active ulcerative colitis (UC). A search query designed by a library informationist was used to identify potential articles for inclusion. Articles were screened and data were extracted by at least two investigators. Outcomes of interest included clinical response, clinical remission, endoscopic response, endoscopic remission, and safety. We identified 28 RCTs for 18 herbs. In pooled analyses, when compared with placebo, clinical response rates were significantly higher for Indigo naturalis (IN) (RR 3.70, 95% CI 1.97-6.95), but not for Curcuma longa (CL) (RR 1.60, 95% CI 0.99-2.58) or Andrographis paniculata (AP) (RR 0.95, 95% CI 0.71-1.26). There was a significantly higher rate of clinical remission for CL (RR 2.58, 95% CI 1.18-5.63), but not for AP (RR 1.31, 95% CI 0.86-2.01). Higher rates of endoscopic response (RR 1.56, 95% CI 1.08-2.26) and remission (RR 19.37, 95% CI 2.71-138.42) were significant for CL. CL has evidence supporting its use as an adjuvant therapy in active UC. Research with larger scale and well-designed RCTs, manufacturing regulations, and education are needed.

Isolation, Characterization, and Expression Analysis of NAC Transcription Factor from Andrographis paniculata (Burm. f.) Nees and Their Role in Andrographolide Production.

Andrographis paniculata (Burm. f.) Nees is an important medicinal plant known for its bioactive compound andrographolide. NAC transcription factors (NAM, ATAF1/2, and CUC2) play a crucial role in secondary metabolite production, stress responses, and plant development through hormonal signaling. In this study, a putative partial transcript of three NAC family genes (ApNAC83, ApNAC21 22 and ApNAC02) was used to isolate full length genes using RACE. Bioinformatics analyses such as protein structure prediction, cis-acting regulatory elements, and gene ontology analysis were performed. Based on in silico predictions, the diterpenoid profiling of the plant's leaves (five-week-old) and the real-time PCR-based expression analysis of isolated NAC genes under abscisic acid (ABA) treatment were performed. Additionally, the expression analysis of isolated NAC genes under MeJA treatment and transient expression in Nicotiana tabacum was performed. Full-length sequences of three members of the NAC transcription factor family, ApNAC83 (1102 bp), ApNAC21 22 (996 bp), and ApNAC02 (1011 bp), were isolated and subjected to the promoter and gene ontology analysis, which indicated their role in transcriptional regulation, DNA binding, ABA-activated signaling, and stress management. It was observed that ABA treatment leads to a higher accumulation of andrographolide and 14-deoxyandrographolide content, along with the upregulation of ApNAC02 (9.6-fold) and the downregulation of ApNAC83 and ApNAC21 22 in the leaves. With methyl jasmonate treatment, ApNAC21 22 expression decreased, while ApNAC02 increased (1.9-fold), with no significant change being observed in ApNAC83. The transient expression of the isolated NAC genes in a heterologous system (Nicotiana benthamiana) demonstrated their functional transcriptional activity, leading to the upregulation of the NtHMGR gene, which is related to the terpene pathway in tobacco. The expression analysis and heterologous expression of ApNAC21 22 and ApNAC02 indicated their role in andrographolide biosynthesis.

Mechanism of antimalarial action and mitigation of infection-mediated mitochondrial dysfunction by phyto-constituents of Andrographis paniculata ((Burm f.) Wall. ex Nees) in Plasmodium berghei-infected mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Andrographis paniculata (AP) ((Burm f.) Wall. ex Nees) is a medicinal plant, documented for its folkloric use in the treatment of malaria. AIM: This study was designed to determine the potency of extract and fractions of A. paniculata (AP) as a curative, both for susceptible and resistant malaria and to also determine the plant's mechanism of action. This study was also designed to determine whether AP extract and its most potent fraction will mitigate infection-mediated mitochondrial dysfunction, and to assess the phytochemical constituents of the most potent fraction. MATERIALS AND METHODS: n-Hexane, dichloromethane, ethylacetate and methanol were used to partition the methanol extract of A. paniculata. Graded doses of these extract and fractions were used to treat mice infected with chloroquine-sensitive strain of P. berghei in a curative model. The most potent fraction was used to treat mice infected with resistant (ANKA strain) P. berghei. Inhibition of hemozoin formation, reversal of mitochondrial dysfunction and antiinflammatory potentials were determined. A combination of ultraperformance liquid chromatography-quadrupole time of flight-mass spectrometry and nuclear magnetic resonance spectroscopy were used for chemical analysis. RESULTS: Microscopy revealed that the dichloromethane fraction decreased the parasite burden the most, and inhibition of the hemozoin formation is one of its mechanisms of action. The dichloromethane fraction reversed parasite-induced mitochondrial pore opening in the host, enzyme-dependent ATP hydrolysis and peroxidation of host mitochondrial membrane phospholipids as well as its antiinflammatory potentials. The UPLC-qTOF-MS report and NMR fingerprints of the dichloromethane fraction of A. paniculata yielded fourteen compounds of which sibiricinone C was identified from the plant for the first time. CONCLUSION: Fractions of A. paniculata possess antiplasmodial effects with the dichloromethane fraction having the highest potency. The potent effect of this fraction may be attributed to the phytochemicals present because it contains terpenes implicated with antimalarial and antiinflammatory activities.

Synergistic action of Hedyotis diffusa Willd and Andrographis paniculata in Nasopharyngeal Carcinoma: Downregulating AKT1 and upregulating VEGFA to curb tumorigenesis.

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.

Inhibition of hepatocellular carcinoma cell proliferation through regulation of the Cell Cycle, AGE-RAGE, and Leptin signaling pathways by a compound formulation comprised of andrographolide, wogonin, and oroxylin A derived from Andrographis Paniculata(Burm.f.) Nees.

ETHNOPHARMACOLOGICAL RELEVANCE: In 2020, liver cancer contributed to approximately 0.9 million new cases and 0.83 million deaths, making it the third leading cause of mortality worldwide. Andrographis paniculata (Burm.f.) Nees(APN), a traditional Chinese or ethnic medicine extensively utilized in Asia, has been historically employed for treating hepatitis and liver cancer. However, the precise molecular mechanism responsible for its therapeutic efficacy remains unclear. AIM OF THE STUDY: To identify and replace the active components of APN on liver cancer, which is investigate the potential of a Multi-Component Chinese Medicine derived from Andrographis paniculata (Burm.f.) Nees(APN-MCCN) for the treatment of liver cancer. MATERIALS AND METHODS: Firstly, the TCMSP database and two liver cancer disease databases were utilized to optimize the chemical constituents of APN and the disease-related targets of liver cancer. The network was constructed using Cytoscape to visualize the relationships between them. Subsequently, the optimal combination of components in APN-MCCN for the treatment of liver cancer was determined using the contribution index method. HPLC analysis was performed to measure the content of each component. Pathway enrichment and gene annotation were conducted using the ClueGo plugin. In vivo efficacy was evaluated by transplanting S180 and H22 tumor-bearing mouse models. In vitro efficacy was determined through MTT assay, morphological observations, flow cytometry analysis, and scratch tests. Western blotting was used to validate the protein expression. The transfection techniques were employed to knockdown the expressions of key protein in different pathway. RESULTS: We obtained 24 effective compounds, with andrographolide contributing 20.78%, wogonin contributing 41.85%, and oroxylin A contributing 30.26% to the overall composition. Based on the predicted enrichment degree and correlation with liver cancer, we identified a total of 27 pathways, among which the Leptin signaling pathway, AGE-RAGE signaling pathway, and Cell Cycle signaling pathway were selected for further investigation. The content of andrographolide, oroxylin A, and wogonin in APN was found to be 0.104%, 0.0024%, and 0.0052%, respectively. In vivo experiments demonstrated that APN-MCCM significantly reduced tumor weight in S180 tumor-bearing mice and prolonged the survival time of H22 liver cancer-bearing mice. APN-MCCM exhibited inhibitory effects on the proliferation, apoptosis, and migration of liver cancer cells while arresting them in the G2/M phase. Furthermore, APN-MCCM down-regulated the protein expression of NCOA1, PTPN1, and GSK3B in the Leptin signaling pathway, NOS2 and NOS3 in the AGE-RAGE signaling pathway, CCNA2, CDK1, CDK2, and CDK7 in the Cell Cycle signaling pathway. Additionally, it upregulated the protein phosphorylation of p-P38 and p-JUN in the AGE-RAGE signaling pathway. Knockout experiments revealed that the inhibitory effect of APN-MCCM on liver cancer cell migration was prevented when the MAPK or NCOA1 genes were knocked out. Similarly, knocking out the CDK7 gene blocked the G2/M phase arrest induced by APN-MCCM in liver cancer cells. CONCLUSIONS: APN-MCCM, consisting of andrographolide, wogonin, and oroxylin A, exhibits inhibitory effects on the cell proliferation of liver cancer cells by targeting the cell cycle pathway. Additionally, it suppresses the migration of liver cancer cells through the AGE-RAGE and Leptin signaling pathways.

Anti-inflammatory effect and pharmacokinetics of dehydroandrographolide, an active component of Andrographis paniculata, on Poly(I:C)-induced acute lung injury.

Acute lung injury (ALI) is a common and critical respiratory disorder caused by various factors, with viral infection being the leading contributor. Dehydroandrographolide (DAP), a constituent of the Chinese herbal plant Andrographis paniculata, exhibits a range of activities including anti-inflammatory, in vitro antiviral and immune-enhancing effects. This study evaluated the anti-inflammatory effects and pharmacokinetics (PK) profile of DAP in ALI mice induced by intratracheal instillation of Poly(I:C) (PIC). The results showed that oral administration of DAP (10-40 mg/kg) effectively suppressed the increase in lung wet-dry weight ratio, total cells, total protein content, accumulation of immune cells, inflammatory cytokines and neutrophil elastase levels in bronchoalveolar lavage fluid of PIC-treated mice. DAP concentrations, determined by an LC-MS/MS method, in plasma after receiving DAP (20 mg/kg) were unchanged compared to those in normal mice. However, DAP concentrations and relative PK parameters in the lungs were significantly altered in PIC-treated mice, exhibiting a relatively higher maximum concentration, larger AUC, and longer elimination half-life than those in the lungs of normal mice. These results demonstrated that DAP could improve lung edema and inflammation in ALI mice, and suggested that lung injury might influence the PK properties of DAP, leading to increased lung distribution and residence. Our study provides evidence that DAP displays significant anti-inflammatory activity against viral lung injury and is more likely to distribute to damaged lung tissue.

Integrating Transcriptome and Chemical Analyses to Provide Insights into Biosynthesis of Terpenoids and Flavonoids in the Medicinal Industrial Crop Andrographis paniculate and Its Antiviral Medicinal Parts.

Andrographis paniculata is a medicinal plant traditionally used to produce diterpene lactones and flavonoids, which possess various biological activities. Widely distributed in China, India, and other Southeast Asia countries, A. paniculata has become an important economic crop, significantly treating SARS-CoV-2, and is being cultivated on a large scale in southern China. The biosynthesis of active ingredients in A. paniculata are regulated and controlled by genes, but their specific roles are still not fully understood. To further explore the growth regulation factors and utilization of its medicinal parts of this industrial crop, chemical and transcriptome analyses were conducted on the roots, stems, and leaves of A. paniculata to identify the biosynthesis pathways and related candidate genes of the active ingredients. The chemical analysis revealed that the main components of A. paniculata were diterpene lactones and flavonoids, which displayed potential ability to treat SARS-CoV-2 through molecular docking. Moreover, the transcriptome sequencing annotated a total of 40,850 unigenes, including 7962 differentially expressed genes. Among these, 120 genes were involved in diterpene lactone biosynthesis and 60 genes were involved in flavonoid biosynthesis. The expression of diterpene lactone-related genes was the highest in leaves and the lowest in roots, consistent with our content determination results. It is speculated that these highly expressed genes in leaves may be involved in the biosynthesis pathway of diterpenes. Furthermore, two class Ⅰ terpene synthases in A. paniculata transcriptome were also annotated, providing reference for the downstream pathway of the diterpene lactone biosynthesis. With their excellent market value, our experiments will promote the study of the biosynthetic genes for active ingredients in A. paniculata and provide insights for subsequent in vitro biosynthesis.

ApCPS2 contributes to medicinal diterpenoid biosynthesis and defense against insect herbivore in Andrographis paniculata.

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.

Enhancing oral bioavailability of andrographolide using solubilizing agents and bioenhancer: comparative pharmacokinetics of Andrographis paniculata formulations in beagle dogs.

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.

Discovery of ent-labdane derivatives from Andrographis paniculata and their anti-inflammatory activity.

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.

Andrographis paniculata and Andrographolide - A Snapshot on Recent Advances in Nano Drug Delivery Systems against Cancer.

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.

Andrographolide, diterpenoid constituent of Andrographis paniculata: Review on botany, phytochemistry, molecular docking analysis, and pharmacology.

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.

Assessment of antidiabetic, anti-inflammatory, antioxidant and anticancer activity competence of methonolic extracts of Trianthema ortulacastrum and Andrographis paniculata.

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.

Harmonizing international quality standards for Andrographis paniculata: A comparative analysis of content determination methods across pharmacopeias.

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.