Regulation of anti-inflammatory and antioxidant responses by methanol extract of Mikania cordata (Burm. f.) B. L. Rob. leaves via the inactivation of NF-κB and MAPK signaling pathways and activation of Nrf2 in LPS-induced RAW 264.7 macrophages.

Mikania cordata (Burm. f.) B.L. Rob. has been traditionally used in tropical countries throughout Asia and Africa to treat gastric ulcers, dyspepsia, and dysentery. However, the mechanisms responsible for its anti-inflammatory and antioxidant activities are not fully understood. Therefore, this study sought to investigate the anti-inflammatory and antioxidant effects of methanol extracts of M. cordata (MMC) on inflammation and oxidative stress in lipopolysaccharide (LPS)-stimulated murine RAW 264.7 macrophages and elucidate its underlying regulatory mechanism. MMC significantly suppressed the production of nitric oxide (NO) and prostaglandin E2 (PGE2) in LPS-stimulated RAW 264.7 macrophages by downregulating the expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) at both the mRNA and protein levels. Moreover, MMC effectively reduced the mRNA expression levels and production of pro-inflammatory cytokines, including interleukin-6 (IL-6), IL-1ß, and tumor necrosis factor-α (TNF-α). These suppressive effects of MMC on pro-inflammatory mediators and cytokines were mediated through the inhibition of transforming growth factor beta-activated kinase 1 (TAK1), which subsequently blocked the activation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPKs). MMC also upregulated the nuclear factor erythroid-2-related factor 2 (Nrf2) by inducing the degradation of Kelch-like ECH-related protein 1 (Keap1), an Nrf2-specific E3 ligase. Accordingly, MMC enhanced Nrf2 target gene expression of anti-oxidative regulators such as heme oxygenase-1 (HO-1) and NAD(P)H quinone oxidoreductase 1 (NQO1). However, it had minimal effect on the DPPH radical scavenging capacity in vitro. Collectively, these findings demonstrate that MMC holds promise as a potential therapeutic agent for alleviating inflammation-related diseases and oxidative stress.

Comparative chloroplast genomics between the invasive weed Mikania micrantha and its indigenous congener Mikania cordata: Structure variation, identification of highly divergent regions, divergence time estimation, and phylogenetic analysis.

Mikania micrantha and Mikania cordata are the only two species in genus Mikania (Asteraceae) in China. They share very similar morphological and life-history characteristics but occupy quite different habitats. Most importantly, they generate totally different ecological consequences. While M. micrantha has become an exotic invasive weed, M. cordata exists as an indigenous species with no harmful effects on native plants or habitats. As a continuous study of our previously reported M. micrantha chloroplast (cp) genome, in this study we have further sequenced the M. cordata cp genome to (1) conduct a comparative genome analysis to gain insights into the mechanism of invasiveness; (2) develop cp markers to examine the population genetic adaptation of M. micrantha; and (3) screen variable genome regions of phylogenetic utility. The M. cordata chloroplast genome is 151,984 bp in length and displays a typical quadripartite structure. The number and distribution of protein coding genes, tRNA genes, and rRNA genes of M. cordata are identical to those of M. micrantha. The main difference lays in that the pseudogenization of ndhF and a 118-bp palindromic repeat only arises in M. cordata. Fourteen highly divergent regions, 235 base substitutions, and 58 indels were identified between the two cp genomes. Phylogenetic inferences revealed a sister relationship between M. micrantha and M. cordata whose divergence was estimated to occur around 1.78 million years ago (MYA). Twelve cpSSR loci were detected to be polymorphic and adopted to survey the genetic adaptation of M. micrantha populations. No cpSSR loci were found to undergo selection. Our results build a foundation to examine the invasive mechanism of Mikania weed.

Multi-functional pharmacological credence of triterpenoid 16-hydroxy betulinicacid isolated from Mikania cordata / 中国药理学与毒理学杂志

OBJECTIVE To isolate and characterize bioactive compound from traditionally impor-tant medicinal plant Mikania cordata,and to investigate muti-faced pharmacological activities of the isolated compound.METHODS A triterpeenoid, 16-hydroxy betulinic acid(16 HBA)was isolated from Mikania cordata leaf and the structure of the compound was determined by NMR spectroscopic means.Antimi-crobial activity of 16 HBA was tested by disc diffusion method and minimum inhibitory concentration (MIC) against the tested microorganisms was determined. The analgesic property of 16 HBA was tested using acetic acid-induced writhes in mice and hot plate thermal stimulation in rats. The anti-inflammatory activity was studied using carrageenin-induced paw edema method. The antipyretic potential of 16 HBA was evaluated by using yeast-induced hyperthermia in rats. RESULTS The triterpenoid 16 HBA showed potent antibacterial activity with inhibition zone of diameter ranging from 12.0~17.5 mm and antifungal activity with mycelial growth inhibition ranges from 37.6%~54.5%.The MIC values for antibacterial and antifungal activities ranged from 31.5~125 and 250~1000 μg·mL-1respectively.The compound(50 and 100 mg·kg-1body weight)showed potent peripheral and central analgesic activity having 55.19% and 41% of writhing inhibition at 90 min after administration of the compound and the highest 55.98%, 79.18% elongation of reaction time,respectively.In anti-inflammatory activity screening,the compound (100 mg·kg-1)revealed the highest 77.08% edema inhibition at 4 h after administration of carrageenan. In antipyretic assay, 16 HBA exhibited a strong antipyretic effect in yeast-induced rats.CONCLUSION The present study confirmed that 16-hydroxy betulinic acid isolated from Mikania cordata has potent anti-microbial,analgesic,anti-inflammatory and antipyretic properties.Our results can be seen as scientific support for the traditional and folklore usage of Mikania cordata in Bangladesh for the treatment of different ailments and provide opportunities to explore this plant as a source bioactive compounds for biochemical and pharmaceutical industries.