جستجوی مقالات مرتبط با کلیدواژه « Andrographolide » در نشریات گروه « پزشکی »

Andrographolide has been studied on different types of human cancer cells, but very few studies have been conducted on oral cancer. The study aimed to evaluate the anticancer potential of Andrographolide on an oral cancer cell line (KB) through in-silico network analysis and in vitro assays.

The in-silico analysis involved the determination of drug-likeness prediction, prediction of common targets between oral cancer and andrographolide, Protein-Protein Interactions (PPI), hub genes, top 10 associated pathways by Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway, Gene Ontology (GO), and molecular docking experiments. In vitro assays comprised MTT assay, apoptosis assay, cell cycle analysis, intracellular reactive oxygen species (ROS) measurement, mitochondrial membrane potential (MMP), anti-migration activity, and gene expressions using Polymerase Chain Reaction (PCR).

Fifteen common genes were obtained and were seen to be involved in cellular proliferation, regulation of apoptosis, migration of cells, regulation of MAPK cascade, and regulation of cell cycle. The most common genes involved in the top 10 pathways were MAPK1, MAPK8, MAPK14, and IL6 which were seen to be associated with the MAPK signaling pathway which may be the key pathway through which andrographolide may aid in treating oral cancer. In vitro assays showed anti-proliferative properties, late apoptosis, and anti-migratory properties.

According to the results obtained, andrographolide has shown anticancer properties and has the potential to be used as a chemotherapeutic drug. The in-silico approach used in the present study can aid as a model for future research in developing efficient cancer treatments.

Paraquat (PQ)-induced acute lung injury (ALI) remains a public concern due to its high mortality. Andrographolide (Andro) has anti-oxidative and anti-apoptosis properties. However, the role of Andro in ALI is still unknown. Herein, the purpose was to explore the function of Andro and potential mechanisms in ALI caused by PQ. An animal model of ALI was established with an intraperitoneal injection of PQ at 20mg/kg. Andro was administered intragastrically for three consecutive days. A specific AMPK inhibitor named Compd C, Nrf2 gene knockout, and a specific PI3K inhibitor named LY294002 were used to clarify the possible mechanism. Results revealed that Andro alleviated PQ-induced histopathological changes, including congestion, hemorrhage, destroyed alveoli, and extracellular matrix deposition, and inhibited apoptosis. Andro up-regulated the p-AMPK/AMPK ratio and Nrf2 and HO-1 levels while decreasing p-PI3K and p-Akt levels. In vitro, Andro appeared to reverse the PQ-induced reductions in SOD and CAT. However, Andro weakened the capacity to promote Nrf2 with Compd C and the capacity to reduce MDA and ROS while increasing SOD and CAT after the Nrf2 gene was knocked out. Additionally, Andro mitigated apoptosis by elevating the Bcl-2/Bax ratio. Results also showed that Andro promoted the Bcl-2/Bax ratio to reduce apoptosis with LY294002. In conclusion, Andro reduces the PQ-induced ALI through the AMPK/Nrf2 and PI3K/Akt pathways. The possible mechanism involves an antioxidant capacity to activate the AMPK/Nrf2 pathway and cause anti-apoptosis suppression of the PI3K/Akt pathway.

Paraquat (PQ), a highly effective and rapidly non-selective herbicide, mainly targets the lungs and causes acute lung injury (ALI). So far, the scarcity of effective drug candidates against PQ-induced ALI remains a big challenge. Andrographolide (Andro), with its anti-inflammatory and antioxidant activities, has been demonstrated to alleviate ALI. Nevertheless, whether Andro could alleviate the PQ-mediated ALI remains unknown. Therefore, this study will explore the effects as well as the possible mechanism of Andro against ALI caused by PQ. 

C57BL/6J mice were injected with 20 mg/kg PQ intraperitoneally to establish an ALI model. PQ-treated MLE-12 cells were applied to a vitro model. Nuclear factor erythroid like-2 (Nrf2) was knocked out to explore the specific effects of the Nrf2/ Heme oxygenase-1 (OH-1) pathway in the protection of Andro against ALI caused by PQ.

Andro significantly reduced lung damage and the ratio of Wet/Dry (W/D) weight, decreased MDA, IL-6, IL-1β, and TNF-ɑ levels, reversed the decrease of CAT and SOD levels, and inhibited apoptosis caused by PQ. Andro obviously increased the ratio of Bcl-2/Bax while reducing caspase-3 and cleaved caspase-3 levels. Furthermore, Andro dramatically elevated the antioxidant proteins Nrf2, NQO-1, and HO-1 levels compared with the PQ group. This experiment demonstrated that Andro reduced ROS and inhibited apoptosis, induced by PQ in MLE-12 cells, by inducing Nrf2/HO-1 pathway activation.

Andro effectively ameliorates oxidant stress and apoptosis in ALI caused by PQ, possibly through inducing Nrf2/HO-1 pathway activation.

Nicotine, a psychoactive compound from the tobacco plant, produces a reward effect that potentially causes addiction. It is postulated that nicotine addiction occurs through increased reactive oxygen species production in nucleus accumbens, which causes damage to the endogenous antioxidant defense system resulting in an increased need for nicotine intake, which leads to addiction. The antioxidants, andrographolide and epigallocatechin gallate (EGCG), are expected as potential substances to decrease the risk of nicotine addiction. This study aimed to analyze the effect of andrographolide and EGCG on the risk of addiction induced by nicotine and cigarette smoke extract (CSE) in mice.

Thirty-five Balb/c male mice, divided into seven groups, were used in this study. The administered drugs were normal saline 1.0 mL/kg BW as control group, nicotine 0.5 mg/kg BW, CSE 1.0 mg/kg BW, andrographolide 50 mg/kg BW, and EGCG 50 mg/kg BW as pre-treatment. Conditioned place preference (CPP) with a biased design method was used to evaluate the reward effects induced by nicotine and CSE. Several stages were carried out, namely pre-conditioning, conditioning, post-conditioning, extinction, and reinstatement tests.

Based on the CPP score, both nicotine (p<0.001) and CSE (p<0.001) groups increased the reward effect significantly compared to that of the normal saline group. The andrographolide + nicotine (p<0.001) and EGCG + nicotine (p<0.001) groups decreased the reward effect significantly compared to that of the nicotine group without pharmacological treatment. Similarly, the andrographolide + CSE (p<0.001) and EGCG + CSE (p<0.01) groups decreased the reward effect significantly compared to that of the CSE group without pharmacological treatment.

Andrographolide and EGCG lower the risk of addiction induced by nicotine and CSE.

The resistance of infectious pathogens to antimicrobial drugs is an underestimated threat to public health. This rapidly developing phenomenon necessitates the discovery of new treatment strategies. Combining natural compounds with first-line antimicrobials is one treatment strategy to mitigate the emergence of resistant pathogens. Andrographolide, a diterpene lactone isolated from Andrographis paniculata has been reported to possess potent anti-infective activity. This study was conducted to evaluate the combination effect of andrographolide with first-line antimicrobial drugs to fight emerging resistance.

The minimum inhibitory concentration (MIC), fold increase in antimicrobial efficacy and fractional inhibitory concentrations (FIC) of andrographolide and ceftriaxone, ciprofloxacin, amoxicillin, metronidazole, amikacin, clindamycin and fluconazole were determined using the high throughput spot culture growth inhibition (HT-SPOTi) assay against ten isolated clinical strains; Streptococcus pyogenes, Escherichia coli, Vibrio cholerae, Pseudomonas aeruginosa, Staphylococcus aureus, Proteus mirabilis, Klebsiella pneumoniae, Enterococcus faecalis, Salmonella paratyphi B and Candida albicans.

Combination of andrographolide and the first-line antimicrobials showed various degrees of susceptibility and efficacy against the tested microorganisms with the highest MIC, 0.85 μg/mL recorded. The FICI (Fractional Inhibitory Concentration Indices) for synergy ranged between 0.00 to 0.28 depending on the microorganism and antimicrobial drug.

Use of andrographolide with first-line antimicrobials could aid in combating the menace of resistance pathogens. However, this should be done with caution as some of the antimicrobials tested exhibited antagonistic effects.

Andrographolide is a phytoconstituent with anti-inflammatory activity, however, the compound’s poor oral bioavailability has hindered its effective formulation for oral administration. This study, therefore, aims to develop an ethosome for improving andrographolide penetration through the transdermal delivery system.

This study developed 3 ethosome formulas with different andrographolide-phospholipid weight ratios (1:8, 1:9 and 1:10), using the thin-layer dispersion-sonication method. Subsequently, the ethosomes were evaluated for particle size, polydispersity index, zeta potential, morphology, as well as entrapment efficiency, and incorporated into a gel dosage form. Subsequently, an in vitro penetration study was performed using Franz diffusion cells for 24 hours and the stability of the gels at 5 ± 2°C, 30 ± 2°C, and 40 ± 2°C, were studied for 3 months.

The results showed the optimal formula was E2, a 1:9 weight ratio formula of andrographolide and phospholipid. Based on the transmission electron micrograph, E2 possessed unilamellar, as well as spherical-shaped vesicles, and exhibited superior characteristics for transdermal delivery, with a particle size of 89.95 ± 0.75 nm, polydispersity index of 0.254 ± 0.020, a zeta potential of -39.3 ± 0.82 mV, and entrapment efficiency of 97.89 ± 0.02%. Furthermore, the cumulative andrographolide penetration and transdermal flux for the ethosomal gel of E2 (EG2) were 129.25 ± 4.66 µg/cm2 and 5.16 ± 0.10 µg/cm2 /hours, respectively. All the ethosomal gel formulations exhibited improved penetration enhancement of andrographolide, compared to the nonethosomal formulations. Also, the andrographolide levels in the ethosomal and nonethosomal gels after 3 months ranged from 98.13 to 104.19%, 97.93 to 104.01%, and 97.23 to 102.26% at storage temperatures of 5 ± 2°C, 30 ± 2°C/RH 65% ± 5%, and 40 ± 2°C/RH 75% ± 5%, respectively.

This study concluded that encapsulation into ethosome enhances andrographolide delivery through the skin.

Herb–drug interactions (HDIs) in pharmacokinetics and pharmacodynamics can occur when natural compounds are used in combination with drugs. This study aimed to review the potential interaction of Andrographis paniculata (Burm. f.) extract (APE) and its primary compound andrographolide (AND) with several drugs exhibiting various pharmacological activities.

In this systematic review, articles were collected from international databases such as PubMed, Science Direct, Springer Link, and Scopus until August 2021. The following keywords were used: Andrographis paniculata, andrographolide, HDI, drug interaction, pharmacokinetics, and pharmacology. This review was written in accordance with the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA), SYRCLE’s risk of bias (RoB) tool for animal intervention studies, and Cochrane RoB 2 tool to analyze the RoB for qualitative assessment.

Twelve articles were included in accordance with the inclusion and exclusion criteria of this study. Five studies explored the potential of HDIs for combining APE with drugs and AND with theophylline, etoricoxib, nabumetone, naproxen, and tolbutamide. Five studies focused on AND in combination with aminophylline and doxofylline, meloxicam, glyburide, glimepiride, metformin, and warfarin. Two studies tested the combination of APE with gliclazide and midazolam. The HDI mechanism involving the inhibition or induction of cytochrome P450 enzyme expression was dominant in influencing the drug’s pharmacokinetic profile. Pharmacological studies on the combination of several drugs, particularly anti-inflammatory and antidiabetic drugs, showed a synergistic activity.

APE and AND have potential pharmacokinetic and pharmacodynamic HDIs with various drugs. This study can be used as a therapeutic consideration in clinical aspects related to the possibility of HDIs of A. paniculata (Burm. f.).

Insulin resistance is a characteristic of non-insulin-dependent diabetes mellitus associated with obesity and caused by the failure of pancreatic beta cells to secrete sufficient amount of insulin. Andrographolide (AND) improves beta-cell reconstruction and inhibits fat-cell formation. This research aimed to improve the delivery of water-insoluble AND in self-nanoemulsifying (ASNE) formulation, tested in streptozotocin (STZ)-induced diabetic rats and 3T3-L1 preadipocyte cells.

A conventional formulation of AND in suspension was used as a control. The experimental rats were orally administered with self-nanoemulsifying (SNE) and suspension of AND for 8 days. Measurements were performed to evaluate blood glucose levels in preprandial and postprandial conditions. Immunohistochemistry was used to assess the process of islet beta cell reconstruction. In vitro study was performed using cell viability and adipocyte differentiation assay to determine the delivery of AND in the formulation.

ASNE lowered blood glucose levels (day 4) faster than AND suspension (day 6). The histological testing showed that ASNE could regenerate pancreatic beta cells. Therefore, ASNE ameliorated pancreatic beta cells. The in vitro evaluation indicated the inhibition of adipocyte differentiation by both AND and ASNE, which occurred in a time-dependent manner. ASNE formulation had better delivery than AND.

ASNE could improve the antidiabetic activity by lowering blood glucose levels, enhancing pancreatic beta cells, and inhibiting lipid formation in adipocyte cells.