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AIM To prepare andrographolide self-microemulsifying drug delivery system.METHODS The range of excipient ratio was determined according to equilibrium solubility,excipient compatibility and pseudo-ternary phase diagram.With Pogostemon cablin oil proportion,Labrasol ALF-Tween 80 ratio and Km as influencing factors,drug loading as an evaluation index,the formulation was optimized by central composite design-response surface method,after which in vitro evaluation was performed.RESULTS The optimized formulation was determined to be 10.45%,13.28%,9.82%,66.44%for Pogostemon cablin oil,Labrasol ALF,Tween 80,Transcutol HP proportions,the equilibrium solubility was(11.95±0.04)mg/g.The quality parameters were(20.22±0.38)s for emulsification time,(51.70±2.91)nm for particle size,0.27±0.02 for polydispersity index,and(91.21±1.58)%for light transmission rate,respectively.The self-microemulsion drug delivery system demonstrated good freeze-thaw stability,whose particle size was not obviously influenced by dilution times and dispersion medium,and was rapidly dissolved in phosphate buffer solution(pH 6.8).CONCLUSION Self-microemulsifying drug delivery system can enhance the solubility and dissolution rate of andrographolide.
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Objective:To investigate the impact of andrographolide (AND) on intestinal inflammation in rats with diarrhea type irritable bowel syndrome (IBS-D) and its regulatory mechanism on the NLRP3/caspase-1 signaling pathway.Methods:After the IBS-D rat model was established by low concentration acetic acid combined with restraint stress, the rats were grouped into control group, model group, positive drug group, AND low-dose (AND-L) group, AND medium dose (AND-M) group, and AND high-dose (AND-H) group, with 10 rats in each group. The score of fecal traits and fecal water content of rats in each group were detected; the abdominal withdrawal reflex (AWR) of rats in each group was scored; HE staining was applied to observe the changes of colonic histopathology of rats in each group; enzyme linked immunosorbent assay (ELISA) was applied to detect the levels of tumor necrosis factor-α (TNF- α), interleukin-6 (IL-6), interleukin-1 β (IL-1 β), and interleukin-18 (IL-18) in the colon tissue of rats in each group; Western blot was applied to detect the expression levels of NLRP3, ASC, and caspase-1 proteins in the colon tissue of rats in each group. Results:The scores of fecal traits of rats in the control group was 2.43±0.19, fecal water content was 31.76±2.81, AWR score was 0.43±0.02, TNF-α was 123.49±12.35, IL-6 was 76.45±6.23, IL-1 β was 195.76±15.14 and IL-18 was 167.31±13.92, the protein expression levels of NLRP3 was 0.96±0.06, ASC was 1.01±0.08, and caspase-1 was 0.94±0.06. The scores of fecal traits in model group was 6.12±0.58, fecal water content was 65.24±4.13, AWR score was 2.42±0.18, which were higher than those in control group ( P<0.05), the TNF- α in model group was 315.73±19.47, IL-6 was 231.97±14.65, IL-1 β was 435.83±28.67, IL-18 was 382.56±26.84, the protein expression levels of NLRP3 was 2.41±0.18, ASC was 2.23±0.15, and caspase-1 was 2.15±0.16, which were higher than those in control group ( P<0.05). The scores of fecal traits in the low, medium, and high dose AND groups were 5.38±0.46, 4.57±0.38, 3.31±0.27, fecal water content were 54.68±3.67, 46.87±3.75, 38.11±3.10, AWR scores were 1.79±0.16, 1.35±0.10, 0.69±0.04, which were higher than those in model group ( P<0.05), the TNF- α in the low, medium, and high dose AND groups were 268.65±17.23, 224.91±16.36, 178.16±14.65, IL-6 were 187.74±14.57, 159.64±11.39, 124.18±8.62, IL-1 β were 369.51±21.96, 314.72±23.64, 263.93±16.82, IL-18 were 334.72±25.17, 280.16±21.43, 235.67±19.32, the protein expression levels of NLRP3 were 1.94±0.15, 1.56±0.12, 1.25±0.09, ASC were 1.89±0.14, 1.61±0.13, 1.28±0.10, and caspase-1 were 1.76±0.14, 1.49±0.11, 1.20±0.09, which were higher than those in model group ( P<0.05) . Conclusion:AND may alleviate intestinal inflammation in IBS-D rats by inhibiting the NLRP3/caspase-1 signaling pathway.
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OBJECTIVE To investigate the impacts of andrographolide on sciatic nerve function injury in diabetic peripheral neuropathy (DPN) rats by regulating high-mobility group protein box 1 (HMGB1)/receptor for advanced glycation end products (RAGE) signal pathway. METHODS A total of 84 rats were randomly divided into the control group (normal saline), DPN group (normal saline), low-dose andrographolide group (0.833 mg/kg), high-dose andrographolide group (3.332 mg/kg), lipoic acid group (positive control, 0.1 g/kg), recombinant rat HMGB1 protein (rHMGB1) group (8 μg/kg), and high-dose andrographolide+ rHMGB1 group, with 12 rats in each group. All rats except those in the control group were fed with high glucose and high fat diet combined with intraperitoneal injections of streptozotocin to establish the DPN rat model. After 24 hours of successful modeling, medication was administered daily for 8 weeks. The changes in fasting blood glucose, mechanical pain threshold, heat pain threshold and sciatic nerve conduction velocity were detected. Pathological changes in the sciatic nerve of rats and the activity of superoxide dismutase (SOD) and the content of malondialdehyde (MDA) in the sciatic nerve of rats were also detected. Besides, the expressions of HMGB1, RAGE proteins and phosphorylation level of nuclear factor κB p65(NF-κB p65) protein in rat sciatic nerves were found. RESULTS Compared with the control group, the pathological damage of the sciatic nerve of rats in the DPN group was strengthened, the fasting blood glucose, heat pain threshold, MDA content and the 诊治。E-mail:dqiaur@163.com expressions of HMGB1, RAGE proteins and phosphorylation level of NF-κB p65 protein were increased (P<0.05), while the mechanical pain threshold, sensory nerve conduction velocity, motor nerve conduction velocity, and SOD activity were decreased/slowed down (P<0.05). Compared with the DPN group, the above indexes were significantly potentiated in the andrographolide low- and high-dose groups and lipoic acid group (P<0.05), and the corresponding trends in the rHMGB1 group were opposite to those in the above three administration groups (P<0.05). Moreover, rHMGB1 attenuated the hypoglycemic effect of high-dose andrographolide on blood glucose and the improvement of oxidative stress injury in the sciatic nerve of DPN rats (P<0.05). CONCLUSIONS Andrographolide may reduce blood glucose by inhibiting the HMGB1/RAGE pathway and oxidative stress, thus ameliorating sciatic nerve injury in DPN rats.
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Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia seen in clinical settings, which has been associated with substantial rates of mortality and morbidity. However, clinically available drugs have limited efficacy and adverse effects. We aimed to investigate the mechanisms of action of andrographolide (Andr) with respect to AF. We used network pharmacology approaches to investigate the possible therapeutic effect of Andr. To define the role of Andr in AF, HL-1 cells were pro-treated with Andr for 1 h before rapid electronic stimulation (RES) and rabbits were pro-treated for 1 d before rapid atrial pacing (RAP). Apoptosis, myofibril degradation, oxidative stress, and inflammation were determined. RNA sequencing (RNA-seq) was performed to investigate the relevant mechanism. Andr treatment attenuated RAP-induced atrial electrophysiological changes, inflammation, oxidative damage, and apoptosis both in vivo and in vitro. RNA-seq indicated that oxidative phosphorylation played an important role. Transmission electron microscopy and adenosine triphosphate (ATP) content assay respectively validated the morphological and functional changes in mitochondria. The translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) to the nucleus and the molecular docking suggested that Andr might exert a therapeutic effect by influencing the Keap1-Nrf2 complex. In conclusions, this study revealed that Andr is a potential preventive therapeutic drug toward AF via activating the translocation of Nrf2 to the nucleus and the upregulation of heme oxygenase-1 (HO-1) to promote mitochondrial bioenergetics.
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Animals , Rabbits , Atrial Fibrillation/metabolism , Kelch-Like ECH-Associated Protein 1/metabolism , Signal Transduction , NF-E2-Related Factor 2/pharmacology , Molecular Docking Simulation , Oxidative Stress , Energy Metabolism , Mitochondria/metabolism , Inflammation/metabolism , Heme Oxygenase-1ABSTRACT
Objective To investigate whether Andrographolide(AG)can alleviate intestinal injury in sepsis by ac-tivating the SLC7A11/GPX4 axis in ferroptosis.Methods Forty rats were randomly divided into sham group(sham group),sepsis group(CLP group),AG low,medium and high dose groups(5,10 and 20 mg/kg).HE staining was used to observe the pathological changes of Intestinal tract.ELISA method was used to determine Inter-leukin 6(IL-6),tumour necrosis factor α(TNF-α),intestinal fatty acid binding protein(I-FABP),D-lactate content.The mechanism of ferroptosis was explored with AG high dose group(AG20 group),forty rats were ran-domly divided into sham group,CLP group,ferroptosis inhibitor(Fer-1)group,AG20+Fer-1 group.HE staining and transmission electron microscopy were used to observe the pathological changes of Intestinal tract.The kits were used to determine oxidative stress MDA,GSH levels and Fe3+content.Western blot was used to detect the protein levels of solute carrier family 7 member 11(SLC7A11),glutathione peroxidase 4(GPX4),and ferritin heavy poly-peptide 1(FTH-1).Results Compared with the sham group,the CLP group showed severe morphological damage to the small intestine,with significantly higher levels of inflammation,I-FABP and D-lactate(all P<0.05),the AG group reversed these changes in a concentration-dependent manner(all P<0.05).Compared with the CLP group,the AG20 and Fer-1 groups showed improved pathological damage to the small intestine,with lower levels of MDA and Fe3+and higher levels of GSH,SLC7A11,GPX4 and FTH-1 protein expression increased(all P<0.05),and pathological injury and oxidative stress were reduced in the AG20+Fer-1 group,and SLC7A11,GPX4 and FTH-1 protein expression increased more significantly(all P<0.05).Conclusion The mechanism by which AG attenuates intestinal injury in sepsis may be related to SLC7A11/GPX4 axis activation in ferroptosis.
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Atherosclerotic cardiovascular disease(ASCVD)frequently results in sudden death and poses a serious threat to public health worldwide.The drugs approved for the prevention and treatment of ASCVD are usually used in combination but are inefficient owing to their side effects and single therapeutic targets.Therefore,the use of natural products in developing drugs for the prevention and treatment of ASCVD has received great scholarly attention.Andrographolide(AG)is a diterpenoid lactone compound extracted from Andrographis paniculata.In addition to its use in conditions such as sore throat,AG can be used to prevent and treat ASCVD.It is different from drugs that are commonly used in the prevention and treatment of ASCVD and can not only treat obesity,diabetes,hyperlipidaemia and ASCVD but also inhibit the pathological process of atherosclerosis(AS)including lipid accumulation,inflammation,oxidative stress and cellular abnormalities by regulating various targets and pathways.However,the pharmaco-logical mechanisms of AG underlying the prevention and treatment of ASCVD have not been corrobo-rated,which may hinder its clinical development and application.Therefore,this review summarizes the physiological and pathological mechanisms underlying the development of ASCVD and the in vivo and in vitro pharmacological effects of AG on the relative risk factors of AS and ASCVD.The findings support the use of the old pharmacological compound('old bottle')as a novel drug('novel wine')for the pre-vention and treatment of ASCVD.Additionally,this review summarizes studies on the availability as well as pharmaceutical and pharmacokinetic properties of AG,aiming to provide more information regarding the clinical application and further research and development of AG.
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OBJECTIVE To investigate the effects of andrographolide (Andro) on angiogenesis in rats with diabetic foot and to explore its mechanism of action based on the Hippo-Yes-associated protein (YAP) signaling pathway. METHODS The rat model of type 2 diabetes was established by using low-dose streptozotocin combined with high-fat and high-glucose diet. On the basis of successful modeling, the rat model of diabetes foot was established by scalding. Model rats were randomly divided into 5 groups with 12 rats in each group: model group, Andro low-dose, medium-dose, and high-dose groups (1, 10, and 20 mg/kg), as well as inhibitor group (20 mg/kg Andro+100 mg/kg of verteporfin, an specific inhibitor of Hippo-YAP signaling pathway); other 12 healthy rats were included in the Control group. Rats in each group were intragastrically and intraperitoneally injected with solvents or corresponding drugs, once a day, for 2 consecutive weeks. The wound healing, fasting blood glucose (FBG) and fasting insulin (FINS) were detected in rats after medication. HE staining was performed to observe the tissue damage and capillary number of rat trauma; the number of endothelial progenitor cells (EPCs) in peripheral blood of rats was counted by using flow cytometry; the contents of serum total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) in rats were determined by fully automatic biochemical analyzer; the expressions of hypoxia- inducible factor 1α (HIF-1α), vascular endothelial growth factor (VEGF) and Hippo-YAP signaling pathway-related proteins in the traumatic tissues of rats in each group were detected by Western blot. RESULTS Compared with Control group, the wound healing rate, capillary number, the proportion of EPCs, HDL-C content, as well as the protein expression levels of HIF-1α and VEGF and the phosphorylation levels of mammalian Ste20-like kinase 1, large tumor suppressor gene 1 and YAP proteins were significantly reduced in the model group, while the FBG, FINS levels and TC, TG and LDL-C contents were significantly increased (P<0.05). Compared with model group, the above indexes were significantly reversed in Andro low-dose, medium-dose and high-dose group, in a dose-dependent manner (P< 0.05); verteporfin attenuated the above reversal effect of Andro (P<0.05). CONCLUSIONS Andro has the effects of lowering blood glucose and blood lipids, promoting blood vessel formation and wound healing in rats with diabetic foot, and its mechanism of action may be related to the activation of Hippo-YAP signaling pathway.
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Objective:To explore the efficacy of andrographolide sulfonate(ADS) nebulized inhalation on pediatric moderate to severe acute respiratory distress syndrome(ARDS) requiring invasive mechanical ventilation.Methods:We conducted a prospective randomized controlled single-blind study.Children with moderate-to-severe ARDS admitted to the PICU at Beijing Children′s Hospital of Capital Medical University from November 1, 2018 to December 31, 2019, aging from 29 days to 18 years, and requiring invasive mechanical ventilation therapy were collected.The experimental group received ADS, while the control group received normal saline.Bronchoalveolar lavage fluid was collected to detect cytokines before and after the experiment.The differences of demography, cytokines and management between two groups were analyzed.Results:Twenty children with a median age of 2.15(1.48, 8.01)years were included and 15(75.00%)cases were boys.Median score of pediatric index of mortality-2 was 12.25(4.53, 16.30). There was no significant differences in demography, basic clinical data and prognosis between two groups( P>0.05). Monocyte chemoattractant protein-1 decreased in the experimental group while increased in the control group with statistic difference[967.50(119.25, 5 206.00)pg/mL vs.-945.00(-3 935.50, 495.09)pg/mL, P=0.041]. Interleukin(IL)-8 decreased in the experimental group but increased in the control group[303.22(-452.00, 1 172.38)pg/mL vs.-490.14(-780.25, 240.52)pg/mL, P=0.151]; and the IL-6 increase of the experimental group was lower than that of the control group[-24.53(-501.76, 135.27)pg/mL vs.-325.85(-633.22, 133.75)pg/mL, P=0.364]; all with no statistic differences( P>0.05). The oxygenation index[11.35(6.00, 15.83) vs.20.65(6.23, 38.35), P=0.374] and the improvement rate of ARDS(80%vs.60%, P=0.628) of the experimental group was better than that of the control group, but with no statistic difference( P>0.05). There was no statistic difference of mortality and mechanical ventilation time between two groups( P>0.05). Conclusion:Inhalation of ADS might reduce the increase of IL-6 and the concentration of monocyte chemoattractant protein-1 and IL-8 in bronchoalveolar lavage fluid of children with ARDS, and might improve pulmonary oxygenation function.Further research is needed to verify the above conclusion.
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OBJECTIVE@#To explore the influences of andrographolide (Andro) on bladder cancer cell lines and a tumor xenograft mouse model bearing 5637 cells.@*METHODS@#For in vitro experiments, T24 cells were stimulated with Andro (0-40 µmol/L) and 5637 cells were stimulated with Andro (0 to 80 µmol/L). Cell growth, migration, and infiltration were assessed using cell counting kit-8, colony formation, wound healing, and transwell assays. Apoptosis rate was examined using flow cytometry. In in vivo study, the antitumor effect of Andro (10 mg/kg) was evaluated by 5637 tumor-bearing mice, and levels of nuclear factor κ B (NF- κ B) and phosphoinositide 3-kinase/AKT related-proteins were determined by immunoblotting.@*RESULTS@#Andro suppressed growth, migration, and infiltraion of bladder cancer cells (P⩽0.05 or P⩽0.01). Additionally, Andro induced intrinsic mitochondria-dependent apoptosis in bladder cancer cell lines. Furthermore, Andro inhibited bladder cancer growth in mice (P⩽0.01). The expression of p65, p-AKT were suppressed by Andro treatment in vitro and in vivo (P⩽0.05 or P⩽0.01).@*CONCLUSIONS@#Andrographolide inhibits proliferation and promotes apoptosis in bladder cancer cells by interfering with NF- κ B and PI3K/AKT signaling in vitro and in vivo.
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Animals , Humans , Mice , Apoptosis , Cell Line, Tumor , Cell Proliferation , Diterpenes/therapeutic use , NF-kappa B/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Urinary Bladder Neoplasms/drug therapyABSTRACT
Gastrointestinal mucositis is one of the most debilitating side effects of the chemotherapeutic agent irinotecan (CPT-11). Andrographolide, a natural bicyclic diterpenoid lactone, has been reported to possess anti-colitis activity. In this study, andrographolide treatment was found to significantly relieve CPT-11-induced colitis in tumor-bearing mice without decreasing the tumor suppression effect of CPT-11. CPT-11 causes DNA damage and the release of double-stranded DNA (dsDNA) from the intestine, leading to cyclic-GMP-AMP synthase (cGAS)‒stimulator of interferon genes (STING)-mediated colitis, which was significantly decreased by andrographolide both in vivo and in vitro. Mechanistic studies revealed that andrographolide could promote homologous recombination (HR) repair and downregulate dsDNA‒cGAS‒STING signaling and contribute to the improvement of CPT-11-induced gastrointestinal mucositis. These results suggest that andrographolide may be a novel agent to relieve gastrointestinal mucositis caused by CPT-11.
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Andrographolide, a diterpene lactone, is the important material basis for the pharmacological effect of the Chinese medicinal Andrographis paniculata (Burm.f.)Nees. Modern pharmacological research has shown that andrographolide has many pharmacological activities such as anti-inflammation, bacteriostat, anti-virus, anti-tumor, protecting liver, promoting the function of gallbladder, and protecting the cardiovascular system and nervous system. It has significant anti-inflammatory activity which involves multiple targets. To be specific, it can inhibit nuclear factor-κB (NF-κB), signal transduction and activator of transcription 3 (STAT3), and other signaling pathways, reduce the synthesis and release of downstream inflammatory mediators, and regulate oxidative stress and immune response to achieve anti-inflammatory effect on various inflammatory diseases. At the same time, it suppresses a variety of tumor cells by inhibiting tumor cell proliferation, blocking cell cycle, and inducing tumor cell apoptosis. Its anti-tumor mechanism involves cellular signaling pathways such as Notch, phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt), NF-κB, and secreted glycoprotein/β-catenin (Wnt/β-catenin). In addition, it can also alleviate diabetes by regulating glucose metabolism. According to related research, it often exerts pharmacological effects through multiple pathways and multiple targets, but the specific targets are unclear. Therefore, this article summarizes the relevant studies on the pharmacological effects and mechanisms of andrographolide in the past three years and puts forward the future research directions, which is expected to serve as a reference for the further in-depth research and development and utilization of andrographolide.
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The plant growth, development, and secondary metabolism are regulated by R2 R3-MYB transcription factors. This study identified the R2 R3-MYB genes in the genome of Andrographis paniculata and analyzed the chromosomal localization, gene structure, and conserved domains, phylogenetic relationship, and promoter cis-acting elements of these R2 R3-MYB genes. Moreover, the gene expression profiles of R2 R3-MYB genes under abiotic stress and hormone treatments were generated by RNA-seq and validated by qRT-PCR. The results showed that A. paniculata contained 73 R2 R3-MYB genes on 21 chromosomes. These members belonged to 34 subfamilies, 19 of which could be classified into the known subfamilies in Arabidopsis thaliana. The 73 R2 R3-MYB members included 36 acidic proteins and 37 basic proteins, with the lengths of 148-887 aa. The domains, motifs, and gene structures of R2 R3-MYBs in A. paniculata were conserved. The promoter regions of these genes contains a variety of cis-acting elements related to the responses to environmental factors and plant hormones including light, ABA, MeJA, and drought. Based on the similarity of functions of R2 R3-MYBs in the same subfamily and the transcription profiles, ApMYB13/21/35/67/73(S22) may regulate drought stress through ABA pathway; ApMYB20(S11) and ApMYB55(S2) may play a role in the response of A. paniculata to high temperature and UV-C stress; ApMYB5(S7) and ApMYB33(S20) may affect the accumulation of andrographolide by regulating the expression of key enzymes in the MEP pathway. This study provides theoretical reference for further research on the functions of R2 R3-MYB genes in A. paniculata and breeding of A. paniculata varieties with high andrographolide content.
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Andrographis paniculata , Gene Expression Regulation, Plant , Genes, myb , Multigene Family , Phylogeny , Plant Proteins/metabolismABSTRACT
Aim To evaluate the effects of androgra- pholide ( Andro) on suppressing tumor growth and improving mitochondrial function on mouse breast cancer and explore its mechanism.Methods MTT assay was performed to measure the effect of Andro on the growth capacity of mouse breast cancer cell line 4T1.Mice were treated with Andro, then tumor volume measured, organ index calculated and Hematoxylin - eosin ( HE ) stained to detect the inhibitory effect of Andro on tumors.Lactate assay kit was used to detect the lactate level in mouse serum to check glycolysis discrepancy.To illustrate the transformation in oxidative phosphorylation ( OXPHOS) , Acetyl coenzyme A ( Acetyl-CoA ) assay kit was used to ascertain Acetyl-CoA content level , Western blot was used to detect the protein expression of pyruvate dehydrogenase ( PDH) , and ATP assay kit was used to ascertain ATP content level.The mitochondria functions were analyzed: oxygen ( ()2 ) consumption was measured by Clark oxygen electrode, and mitochondrial membrane potential was detected by JC-1 staining.Results Andro could effectively inhibit the proliferation of 4T1 cells and the growth of tumors, and had no significant damage on normal organs.An- clro reduced serum lactic acid content, indicateing that Andro inhibited the process of glycolysis.The expression of PDH, content of acetyl-CoA and ATP content increased with the increase of Andro concentration.It showed that Andro could up-regulate oxidative phosphorylation.In addition, the ()2 consumption and mitochondrial membrane potential increased in 4T1 cells, indicating that Andro could recover mitochondrial function.Conclusions Andro can inhibit the growth of mouse breast cancer, and its mechanism may be related to the inhibition of glycolysis level, restoration of OXPHOS and improvement of mitochondrial function.
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Abstract In the work the andrographolide (AG)-solid dispersions (SDs) were prepared by the spray-drying method, using polyethylene glycol 8000 (PEG8000), Poloxamer188, polyvinylpyrrolidone K30 (PVPK30), Soluplus® as carrier materials. The effect of different polymers as carrier materials on the properties of the AG-SDs were studied. The results showed obvious differences in intermolecular interaction, thermal stability, drug state, powder properties, dissolution behavior, and so on of AG-SDs prepared using different polymers as carrier materials. AG-PEG8000-SD was a partial-crystalline and partial-amorphous powder with smaller surface area and pore volume, but it was easy to wetting and did not swell in contact with dissolved medium. AG-Soluplus®-SD was completely amorphous powder with larger specific surface area and pore volume, but it swelled in contact with water. Therefore, the dissolution profile of AG in AG-PEG8000-SD was similar to that in AG-Soluplus®-SD. Soluplus® and PEG8000 were suitable polymers to design AG-SDs, considering both physicochemical properties and dissolution behaviors. The results of this reseach showed that when selecting carrier materials for SD, we should not only consider the state of drugs in SD and the powder properties of SD, but also consider whether there is swelling when the carrier materials are in contact with the dissolution medium.
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Polyethylene Glycols/adverse effects , Dissolution , Methods , Polymers/analysis , Pharmaceutical Preparations/analysis , Water , Spray DryingABSTRACT
One-sixth of the currently known natural products contain α, β-unsaturated carbonyl groups. Our previous studies reported a rare C-sulfonate metabolic pathway. Sulfonate groups were linked to the β-carbon of α, β-unsaturated carbonyl-based natural compounds through this pathway. However, the mechanism of this type of metabolism is still not fully understood, especially whether it is formed through enzyme-mediated biotransformation or direct sulfite addition. In this work, the enzyme-mediated and non-enzymatic pathways were studied. First, the sulfite content in rat intestine was determined by LC-MS/MS. The results showed that the amount of sulfite in rat intestinal contents was from 41.5 to 383 μg·g
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Objective: To investigate the mechanisms of andrographolide against non-alcoholic steatohepatitis (NASH) based on network pharmacology, so as to provide a reference for further study of andrographolide in the treatment of NASH and other metabolic diseases. Methods: The methionine- and choline-deficient (MCD) diet-induced NASH mice were treated by administration of andrographolide, and serum transaminase and pathological changes were analyzed. The network pharmacology-based bioinformatic strategy was then used to search the potential targets, construct protein–protein interaction (PPI) network, analyze gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment, and conduct molecular docking to explore the molecular mechanisms. Results: The predicted core targets TNF, MAPK8, IL6, IL1B and AKT1 were enriched in non-alcoholic fatty liver disease (NAFLD) signaling pathway and against NASH by regulation of de novo fatty acids synthesis, anti-inflammation and anti-oxidation. Conclusion: This work provides a scientific basis for further demonstration of the anti-NASH mechanisms of andrographolide.
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This paper mainly studied the effect of Xiyanping injection on the bacterial endotoxin lipopolysaccharide (LPS)-induced fever in rabbits, preliminarily investigated the mechanisms, and provided pharmacological basis for the clinical application. The rabbit model of endotoxin-induced fever was established by using LPS as the inducer; The changes of rectal temperature were measured; The levels of prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and phospholipaseA2 (PLA2) in the serum were measured; The levels of PGE2, cyclic adenosine monophosphate (cAMP), and arginine vasopressin (AVP) in cerebrospinal fluid as well as hypothalamus were detected. The animal welfare and experimental process are in accordance with the regulations of the Animal Ethics Committee of China Pharmaceutical University in this study. The results showed that Xiyanping injection (12.5, 25, and 50 mg·kg-1) could significantly reduce LPS-upregulated body temperature of rabbits, and the duration of action could reach 5.5-8.5 h. At the doses of 25 and 50 mg·kg-1, the antipyretic effect of Xiyanping injection was comparable to that of analgin injection (50 mg·kg-1). Furthermore, Xiyanping injection and analgin injection both reduced the levels of PGE2, IL-1β, TNF-α, and PLA2 in the serum of febrile rabbits to the varying degrees. In addition, Xiyanping injection also down-regulated the levels of PGE2, cAMP, and AVP in the hypothalamus, and PGE2 and cAMP in the cerebrospinal fluid. The level of AVP in the cerebrospinal fluid was up-regulated. This study indicated that Xiyanping injection could significantly improve the endotoxin-induced fever in rabbits, and mechanisms were closely related to the regulation of the levels of PGE2, TNF-α, IL-1β, PLA2, cAMP, and AVP in serum, hypothalamus, and cerebrospinal fluid.
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Objective: To investigate the effect of HPMC, PVP k30 and PEG 4000 on the phase behavior of andrographolide self-nanoemulsifying drug delivery system (AG-SNEDDS) dispersed in Fasted-state simulated intestinal fluid (FaSSIF). Methods: The preparation technology of andrographolide AG-SNEDDS was optimized by central composite design. The effect of three types of precipitation inhibitors (PVP-k30, HPMC, PEG 4000) on the supersaturation behavior of AG-SNEDDS dispersed in FaSSIF was investigated with the degree of supersaturation as an evaluation index. The precipitated phase was evaluated by polarized light microscopy (PLM). Results: The results showed that the best prescription of AG-SNEDDS was Capryol 90-Cremophor EL:Tween-20 (1:1)-Transcutol HP (12.9:40.5:46.6). The self-microemulsion was uniform, the drug loading was (6.93 ± 0.04) mg/g. The emulsification time was (22.33 ± 0.33) s, the average particle size was (14.25 ± 0.65) nm. HPMC and PEG 4000 can maintain the supersaturation of AG-SNEDDS after being dispersed in FaSSIF, and the effect was positively correlated with their concentration. As for PVP k30, it reduced the degree of supersaturation at a low concentration, but can maintain supersaturation at medium and high concentration. Using any of the three precipitation inhibitors can reduce the particle size of the precipitated particles. Conclusion: Precipitation inhibitors can maintain the supersaturation of AG when disperse AG-SNEDDS in FaSSIF. The ability to maintain supersaturation varies with the types and concentration of precipitation inhibitor.
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Since December 2019, coronavirus disease 2019 (COVID-19) has spread rapidly in China. National Health Commission of the People’s Republic of China and local departments have released a number of diagnosis and treatment plans for COVID-19. Some plans recommend Xiyanping Injection for the clinical treatment of COVID-19. The active component of the drug is the total sulfonate of andrographolide, which is a derivative of andrographolide. This paper summarized the pharmacological action and clinical application of andrographolide, and proposed that it has the functions of clearing heat and detoxification, anti-bacterial and anti-inflammatory, and definite therapeutic effect on respiratory system diseases including viral pneumonia and upper respiratory tract infection, and a large number of clinical data have been accumulated. Andrographolide has a potential antiviral effect on the treatment of COVID-19, and can reduce the level of inflammation in patients, improve respiratory symptoms, inhibit concurrent bacterial infection, and improve the body immunity. At the same time, it will not bring the immunosuppressive effect of hormone drugs, and the incidence of adverse reactions is low. In addition, Andrographolide has certain hepatoprotective effects and clinical value for treating cardiovascular diseases in clinical experience, suggesting that it may have some protective effects on drug-induced liver injury, heart injury and liver injury caused by durgs against COVID-19, but further clinical verification is needed. The pharmacological action and clinical application of andrographolide are summarized. This paper also analyzes the etiology, pathogenesis and dialectical treatment of COVID-19 from the perspective of traditional Chinese medicine, and points out that the treatment of COVID-19 with andrographolide is consistent with the theory of traditional Chinese medicine.
ABSTRACT
Dengue is a debilitating disease that poses a perpetual threat to human health and increases the global economic burden every year. Despite advances in medical sciences, dengue virus (DENV) infects approximately 200 million people every year. To date, no effective antiviral is valiable to treat DENV in individuals despite great efforts in accomplishing these goals. Numerous approaches have been used in the search for dengue antiviral like screening of combinatorial compounds against DENV enzymes and structure-based computational discovery. In recent years, investigators have turned their focus into medicinal plants, trying to identify compounds that can be used as dengue antiviral. Nature represents a great reservoir of potential substances that can be explored with the aim of discovering new drugs that can be either used directly as pharmaceuticals or can provide drug leads, which can be scrutinized further for the development of new anti-dengue natural product. Many previous investigations have dealt with numerous plant extracts or bioactive principles for their antiviral property as they normally considered being safer when compared to synthetic drugs. Andrographis paniculata belongs to family Acanthaceae and is generally known as 'king of bitters'. Diverse bioactive compounds from this plant such as diterpenes, flavonoids, xanthones, noriridoides and other miscellaneous compounds have exhibited their potential as therapeutics for various chronic as well as infectious diseases. This review is based on literature review on scientific journals, books and electronic sources, which highlights the pathogenesis of DENV and describe an assortment of bioactive principles that have been possessing antiviral potential, which include dengue and discuss the therapeutic efficacy and mechanism of action of Andrographis paniculata. However, a detailed and more comprehensive clinical trial on mammalian tissues and organs is needed in future studies.