Pharmacological Action of Baicalin on Gestational Diabetes Mellitus in Pregnant Animals Induced by Streptozotocin via AGE-RAGE Signaling Pathway.

OBJECTIVE: Baicalin (BC) is a flavonoid reported to have various pharmacological activities, including antioxidant, anti-cancer, anti-inflammatory, anti-allergy, immune regulation, and anti-diabetic. This study examines the probable mechanism for gestational diabetes mellitus (GDM) brought on by streptozotocin (STZ) and the impact of BC on fetal development via AGEs (advanced serum glycation end products) and RAGE (the role of advanced glycation end products). MATERIAL AND METHOD: STZ has been used in the current experimental study to induce diabetes mellitus in pregnant animals (gestational diabetes mellitus). GDM pregnant animals were separated into five groups and were treated with BC in a dose-dependent pattern for 19 days. At the end of the experiment, the fetus and blood samples were drawn from all the pregnant rats to assess the biochemical parameter as well as AGE-RAGE. RESULT: Administration of BC at varying doses leads to enhancement in the weight of the fetus body and placenta while gestational diabetic pregnant animals induced by STZ had a lower weight of the fetus body and placenta. The dose-dependent pattern of BC also enhanced fasting insulin (FINS), high-density lipoprotein (HDL), serum insulin, and hepatic glycogen. It also significantly enhanced the content of the antioxidant profile and pro-inflammatory cytokines and modulated the gene expression (VCAM- 1, p65, EGFR, MCP-1, 1NOX2, and RAGE) in various tissues in gestational diabetes mellitus pregnant rats. CONCLUSION: Baicalin demonstrated the potential impact on the embryo's development via the AGE-RAGE signaling pathway in STZ-induced GDM pregnant animals.

Triptonide, a Diterpenoid Displayed Anti-Inflammation, Antinociceptive, and Anti-Asthmatic Efficacy in Ovalbumin-Induced Mouse Model.

The present study was intended to explore the valuable effects of triptonide on inflammation, asthmatic, and nociceptive. Triptonide possesses numerous beneficial effects extensively managed in the treatment of inflammation disease condition. Initially, triptonide showed anti-inflammation properties over lipopolysaccharide-induced RAW 264.7 cells. Hence, the present study was directed to explore the protecting efficacy of triptonide in ovalbumin (OVA)-induced asthma in mice. Asthma was induced intraperitoneally administration (200µL) in female BALB/c mice with suspension which has ovalbumin (100 µg/mL) and aluminum hydroxide (10 mg/mL). Triptonide (30 mg/kg) over OVA-induced experimental animals altered lung mass, nitric oxide, myeloperoxidase, immunoglobulin E status, interleukins (4, 5, and 13) inflammatory cytokines status, and histological modifications. Animals were also managed with the standard drug dexamethasone (50 mg/kg) followed by the asthma induction, which is also efficient over OVA-induced experimental animals. The nociception was provoked in male Swiss mice by various chemicals (acetic acid, capsaicin, and glutamate). The animals were administered with triptonide (5, 10, and 15 mg/kg) and separate standard drugs like diclofenac sodium (10 mg/kg) and morphine (5 mg/kg) over chemical-induced nociceptive animals. The present outcome evidently established that the triptonide considerably reduced the various chemical-induced nociception in mice (Fig. 7A, B, and C). Ultimately, the present work explored the evident powerful anti-inflammation, antinociceptive, and anti-asthma properties of a diterpenoid, triptonide experimental animal models. And it is recommended that triptonide is an excellent compound in the management of asthma and its related diseases.

Alleviation of isoprenaline hydrochloride induced myocardial ischemia injury by brucine through the inhibition of Na+/K+-ATPase.

Myocardial infarction (MI) is the most extensive manifestations of cardiovascular disease (CVD), associated with prolonged supply and demand blood oxygen imbalance to the heart muscle. The treatment of MI includes several conventional medicines which are beta-blockers and calcium antagonists. Though, these were reported to be either not efficient or associated with life threatening adverse effects. Brucine, the main alkaloid bioactive compound from Strychnos nux-vomica seeds, offers unique compatibility advantages in inflammatory diseases associated clinical practices. Thus, the present investigation was projected to explore the activity of brucine towards MI provoked by isoprenaline hydrochloride (ISO) in rats. The cardioprotective properties of brucine were evaluated via detecting the infarct size, serum cardiac marker enzymes (CK, CK-MB, cTnT, and cTnI), endogenous antioxidants (CAT, SOD, GPx), and lipid peroxidation (TBARS and LOOH), inflammatory mediators (NF-κB, TNF-α and IL-6) and histopathological analysis. The results demonstrated, brucine effectively restored the infarct size by increasing the endogenous antioxidants and decreasing the status of TBARS and LOOH, marker enzymes and ameliorated the histopathological injuries. Brucine's cardioprotective effect might be associated with TNF-α, IL-6 signaling molecules activation, revealing its pharmacological actions.

Evaluation of antiarthritic activity of nimbolide against Freund's adjuvant induced arthritis in rats.

Nimbolide, a triterpenoid isolated from flower of neem tree possess various therapeutic properties. The objective of the study was to assess the anti-arthritic activity of nimbolide in arthritis induced rats. Nimbolide (20 mg/kg per day) was given orally to arthritic rats induced with Complete Freund's Adjuvant and changes in paw volume, body weight, organ indices (thymus and spleen), arthritic score, biochemical parameters and proinflammatory cytokines levels were determined. Histopathological analysis was also performed. Western blot analysis was also performed. Rats treated with nimbolide displayed marked reduction in arthritic score, organ indices, volume of paw, edema formation, along with substantial enhancement in body weight. Histopathological findings showed significant reduction in destruction of joints and inflammation following nimbolide treatment. The protective action of arthritic rats treated with nimbolide was also substantiated by molecular and biochemical studies. The results of the study show that nimbolide treatment has markedly enhanced health and reduced inflammation via lessening the proinflammatory cytokines expression in arthritic rats. Hence, nimbolide may be used as a potent therapeutic drug in treating rheumatoid arthritis.

Transcriptome sequencing and expression analysis of terpenoid biosynthesis genes in Litsea cubeba.

BACKGROUND: Aromatic essential oils extracted from fresh fruits of Litsea cubeba (Lour.) Pers., have diverse medical and economic values. The dominant components in these essential oils are monoterpenes and sesquiterpenes. Understanding the molecular mechanisms of terpenoid biosynthesis is essential for improving the yield and quality of terpenes. However, the 40 available L. cubeba nucleotide sequences in the public databases are insufficient for studying the molecular mechanisms. Thus, high-throughput transcriptome sequencing of L. cubeba is necessary to generate large quantities of transcript sequences for the purpose of gene discovery, especially terpenoid biosynthesis related genes. RESULTS: Using Illumina paired-end sequencing, approximately 23.5 million high-quality reads were generated. De novo assembly yielded 68,648 unigenes with an average length of 834 bp. A total of 38,439 (56%) unigenes were annotated for their functions, and 35,732 and 25,806 unigenes could be aligned to the GO and COG database, respectively. By searching against the Kyoto Encyclopedia of Genes and Genomes Pathway database (KEGG), 16,130 unigenes were assigned to 297 KEGG pathways, and 61 unigenes, which contained the mevalonate and 2-C-methyl-D-erythritol 4-phosphate pathways, could be related to terpenoid backbone biosynthesis. Of the 12,963 unigenes, 285 were annotated to the terpenoid pathways using the PlantCyc database. Additionally, 14 terpene synthase genes were identified from the transcriptome. The expression patterns of the 16 genes related to terpenoid biosynthesis were analyzed by RT-qPCR to explore their putative functions. CONCLUSION: RNA sequencing was effective in identifying a large quantity of sequence information. To our knowledge, this study is the first exploration of the L. cubeba transcriptome, and the substantial amount of transcripts obtained will accelerate the understanding of the molecular mechanisms of essential oils biosynthesis. The results may help improve future genetic and genomics studies on the molecular mechanisms behind the chemical composition of essential oils in L. cubeba fruits.

Identification of appropriate reference genes for normalizing transcript expression by quantitative real-time PCR in Litsea cubeba.

Quantitative real-time PCR has emerged as a highly sensitive and widely used method for detection of gene expression profiles, via which accurate detection depends on reliable normalization. Since no single control is appropriate for all experimental treatments, it is generally advocated to select suitable internal controls prior to use for normalization. This study reported the evaluation of the expression stability of twelve potential reference genes in different tissue/organs and six fruit developmental stages of Litsea cubeba in order to screen the superior internal reference genes for data normalization. Two softwares-geNorm, and NormFinder-were used to identify stability of these candidate genes. The cycle threshold difference and coefficient of variance were also calculated to evaluate the expression stability of candidate genes. F-BOX, EF1α, UBC, and TUA were selected as the most stable reference genes across 11 sample pools. F-BOX, EF1α, and EIF4α exhibited the highest expression stability in different tissue/organs and different fruit developmental stages. Besides, a combination of two stable reference genes would be sufficient for gene expression normalization in different fruit developmental stages. In addition, the relative expression profiles of DXS and DXR were evaluated by EF1α, UBC, and SAMDC. The results further validated the reliability of stable reference genes and also highlighted the importance of selecting suitable internal controls for L. cubeba. These reference genes will be of great importance for transcript normalization in future gene expression studies on L. cubeba.