Review of phytomedicine, phytochemistry, ethnopharmacology, toxicology, and pharmacological activities of Cymbopogon genus.

The Cymbopogon genus belongs to the Andropoganeae family of the family Poaceae, which is famous for its high essential oil concentration. Cymbopogon possesses a diverse set of characteristics that supports its applications in cosmetic, pharmaceuticals and phytotherapy. The purpose of this review is to summarize and connect the evidence supporting the use of phytotherapy, phytomedicine, phytochemistry, ethnopharmacology, toxicology, pharmacological activities, and quality control of the Cymbopogon species and their extracts. To ensure the successful completion of this review, data and studies relating to this review were strategically searched and obtained from scientific databases like PubMed, Google Scholar, ResearchGate, ScienceDirect, and Elsevier. Approximately 120 acceptable reviews, original research articles, and other observational studies were included and incorporated for further analysis. Studies showed that the genus Cymbopogon mainly contained flavonoids and phenolic compounds, which were the pivotal pharmacological active ingredients. When combined with the complex ß-cyclodextrin, phytochemicals such as citronellal have been shown to have their own mechanism of action in inhibiting the descending pain pathway. Another mechanism of action described in this review is that of geraniol and citral phytochemicals, which have rose and lemon-like scents and can be exploited in soaps, detergents, mouthwash, cosmetics, and other products. Many other pharmacological effects, such as anti-protozoal, anti-bacterial, anti-inflammatory and anti-cancer have been discussed sequentially, along with how and which phytochemicals are responsible for the observed effect. Cymbopogon species have proven to be extremely valuable, with many applications. Its phytotherapy is proven to be due to its rich phytochemicals, obtained from different parts of the plant like leaves, roots, aerial parts, rhizomes, and even its essential oils. For herbs of Cymbopogon genus as a characteristic plant therapy, significant research is required to ensure their efficacy and safety for a variety of ailments.

Lycium barbarum polysaccharides attenuates high glucose-induced diabetic retinal angiogenesis by rescuing the expression of miR-15a-5p in RF/6A cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Lycium barbarum L., a classical traditional Chinese Medicine, has long been used to treat ocular diseases. Lycium barbarum polysaccharides (LBP) is an effective component of Lycium barbarum L. with a wide range of pharmacological activities. This research aims to investigate the inhibition of high glucose-induced angiogenesis by LBP in RF/6A cells. MATERIALS AND METHODS: A high-glucose-induced angiogenesis model was established using monkey retinal vascular endothelial (RF/6A) cells. Different dosages administration times of LBP and glucose concentrations were tested. Under the optimized conditions, RF/6A cells were treated with LBP for 48 h, followed by another 48-h culture in high glucose (25 mmol/L) medium. The effect and mechanism of LBP were investigated following the treatment. RESULTS: The expression of miR-15a-5p and miR-15a-3p in RF/6A cells decreased significantly after 48 h of 25 or 50 mmol/L high glucose treatment. The expression of miR-15a-5p was higher than that of miR-15a-3p. Mimic-miR-15a-5p or 600 mg/L LBP could increase the apoptosis of cells and the total length of vascular branches. The expression of VEGFA, VEGFR2, and ANG2 proteins was reduced, while the expression of ANG1 protein was elevated. Expression of ASM mRNA and protein was also inhibited. CONCLUSIONS: LBP attenuates diabetic retinal angiogenesis by rescuing the expression of miR-15a-5p in RF/6A cells.

Dehydrocostuslactone attenuated oxygen and glucose deprivation/reperfusion-induced PC12 cell injury through inhibition of apoptosis and autophagy by activating the PI3K/AKT/mTOR pathway.

The purpose of this study is to investigate the protective effect of dehydrocostuslactone (DHL) on PC12 cells injury induced by oxygen and glucose deprivation/reperfusion (OGD/R) and its possible mechanism on the PI3K/AKT/mTOR pathway. The maestro 11.1 software was used to predict the binding sites of DHL with LC3, Beclin-1, PI3K, AKT, mTOR, Bax, Bcl-2, Caspase-3, Caspase-9, and Caspase-7. We used a cellular model of 2 h of OGD and 24 h of reperfusion to mimic cerebral ischemia-reperfusion injury. Cells were treated with DHL during the reperfusion phase. The docking results showed that DHL had binding sites with LC3, Beclin-1, PI3K, AKT, mTOR, Bax, Bcl-2, Caspase-3, Caspase-9, and Caspase-7. The expression levels of autophagy-related proteins, LC3 and Beclin-1 increased while P-PI3K, P-AKT, and P-mTOR decreased. Apoptosis-related proteins, namely, Bax, Cyto-c, Caspase-3, Caspase-7, Caspase-9 increased, but the anti-apoptosis Bcl-2 protein decreased. However, DHL effectively inhibited these undesirable changes induced by OGD/R in PC12 cells. Our results suggested that DHL attenuated OGD/R-induced neuronal injury by inhibiting apoptosis and autophagy by activating PI3K/AKT/mTOR signaling. This inhibition can improve cell survival and offer evidence for the beneficial effects of DHL on the nervous system.

Costunolide attenuates oxygen­glucose deprivation/reperfusion­induced mitochondrial­mediated apoptosis in PC12 cells.

The present study investigated the effect of costunolide (CT), a compound extracted from Aucklandia lappa Decne, to attenuate oxygen­glucose deprivation/reperfusion (OGD/R)­induced mitochondrial­mediated apoptosis in PC12 cells. The present study used molecular docking technology to detect the binding of CT with mitochondrial apoptotic protein targets. A model of oxygen­glucose deprivation for 2 h and reperfusion for 24 h in PC12 cells was used to mimic cerebral ischemic injury. Cell viability and damage were measured using the Cell Counting kit­8 and lactate dehydrogenase (LDH) cytotoxicity assay kits. Cellular apoptosis was analyzed using flow cytometry. A fluorescence microscope determined intracellular [Ca2+] and mitochondrial membrane potential. Furthermore, immunofluorescence and Western blot analyses were used to detect the expression of apoptosis­associated proteins. CT contains binding sites with Caspase­3, Caspase­9 and Caspase­7. CT markedly enhanced cell viability, inhibited LDH leakage, increased intracellular [Ca2+], stabilized the mitochondrial membrane potential, increased the expression of Bcl­2 and inhibited the expression of Apaf­1, Bax, cleaved­caspase­7, cleaved­caspase­9 and cleaved­caspase­3. CT may markedly protect PC12 cells from damage caused by OGD/R, and its mechanism is associated with blocking the calcium channel and inhibiting mitochondrial­mediated apoptosis.

Mu-Xiang-You-Fang protects PC12 cells against OGD/R-induced autophagy via the AMPK/mTOR signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Mu-Xiang-You-Fang (MXYF) is a classic prescription of Hui medicine. It is composed of five herbs and has been used to treat ischemic stroke for many years. However, the potential pharmacological mechanisms of MXYF remain unclear. The present research is aimed to investigate the protective effect and possible mechanisms of MXYF treatment in an in vitro model of cerebral ischemia-reperfusion injury. MATERIALS AND METHODS: An oxygen-glucose deprivation and reperfusion (OGD/R) model of PC12 cells was established. The effect of MXYF on the cell viability after OGD/R injury was determined using a cell counting kit (CCK-8) assay. The colorimetric method was used to determine the lactate dehydrogenase (LDH) leakage rate. The calcium concentration was determined by the chemical fluorescence method, and mitochondrial membrane potential was determined using flow cytometry. Monodansylcadaverine (MDC) staining and electron microscopic analysis were then conducted to detect autophagy after oxygen-glucose deprivation and reperfusion in PC12 cells. Immunofluorescence and western blot analyses were used to detect the expression of proteins associated with autophagy. RESULTS: It was found that MXYF (1, 2, 4 µg/mL) could significantly increase cell viability and mitochondrial membrane potential and decrease the calcium concentration and LDH release rate in PC12 cells. After OGD/R injury in PC12 cells, the number of autophagosomes and autophagolysosome significantly increased. MXYF (4 µg/mL) inhibited the autophagy induced by OGD/R and inhibited the expression of LC3, beclin1, p-AMPK, and ULK1. In contrast, the expression of p-mTOR, p-p70s6k, and p62 was significantly enhanced. CONCLUSIONS: These findings suggest that MXYF inhibits autophagy after OGD/R-induced PC12 cell injury through the AMPK-mTOR pathway. Thus, MXYF might have therapeutic potential in treating ischemic stroke.

Cynomorium songaricum prevents bone resorption in ovariectomized rats through RANKL/RANK/TRAF6 mediated suppression of PI3K/AKT and NF-κB pathways.

AIM: Cynomorium songaricum Rupr., an edible and important Traditional Chinese medicine has long been used in folk for treatment of kidney deficiency, was chosen to estimate the antiosteoporotic activity and underlying molecular mechanism on rats induced by ovariectomy (OVX). MAIN METHODS: 9 of 45 rats were underwent bilateral laparotomy without removing the ovaries as sham group, remains were underwent bilateral ovariectomy and equally randomized into four groups: with vehicle (0.5% CMC-Na) as model group, estradiol valerate (1 mg/kg body weight/day) as positive control, with 100 and 300 mg/kg body weight/day of ethanol extracts of C. songaricum extract (CSE) as low and high dosage groups, respectively. KEY FINDINGS: After 12 weeks of continues orally intervention, the decreases of bone mineral density, bone mineral content, tissue mineral content, as well as the increases of bone trabecular separation and bone resorption markers were significantly reversed by CSE in the OVX rats, and in particular, a contradictory phenomenon on calcium and phosphorus contents was observed and elucidated. Mechanistically, the expressions of tumor-necrosis factor receptor-associated factor 6 (TRAF 6), nuclear factor kappa B (RANK) and its ligand (RANKL), as well as the nuclear factor kappa B (NF-κB), phosphoinositide 3­kinase (PI3K) and protein kinase B (AKT) levels were significantly down-regulated by CSE intervention, whereas the osteoprotegerin (OPG) was significantly up-regulated by CSE as compared to the control. SIGNIFICANCE: Concisely, C. songaricum exhibited potential therapeutic effect on bone metabolism of ovariectomized rats, and this effect was possibly exerted by RANKL/RANK/TRAF6 mediated down-regulation of NF-κB and PI3K/AKT pathways.

Protective effects of dehydrocostuslactone on rat hippocampal slice injury induced by oxygen­glucose deprivation/reoxygenation.

The present study aimed to investigate the protective effects of dehydrocostuslactone (DHL) against rat hippocampal slice injury caused by oxygen­glucose deprivation/reoxygenation (OGD/R). Rat hippocampal slice injury was induced by OGD/R in vitro, and the degree of injury was evaluated through a lactate dehydrogenase (LDH) assay and 2,3,5­triphenyltetrazolium chloride (TTC) staining. The protein expression levels of B­cell lymphoma-2 (Bcl­2), Bcl­2­associated X protein (Bax), cytochrome c (cyt­c), apoptotic protease activating factor 1 (apaf­1), caspase­9, caspase­7, caspase­3, sequestosome 1 (SQSTM1) and microtubule­associated protein 1 light chain 3 (LC3) were analyzed through western blot analysis. The results showed that 1, 5 and 10 µM DHL decreased the levels of LDH (P<0.05) and increased the A490 value of TTC (P<0.05). Furthermore, the expression of Bcl­2 was enhanced, and the protein expression levels of Bax, cyt­c, apaf­1, caspase­9, caspase­7, caspase­3, SQSTM1 and LC3 were significantly inhibited (P<0.05), compared with those in the OGD/R group. These results suggested that DHL elicited protective effects against hippocampal OGD/R injury, and its underlying mechanism may be associated with inhibiting apoptosis.

Syringin prevents bone loss in ovariectomized mice via TRAF6 mediated inhibition of NF-κB and stimulation of PI3K/AKT.

BACKGROUND: Syringin, also called eleutheroside B, is a main bioactive phenolic glycoside in Acanthopanax senticosus (Rupr. et Maxim.) Harms. Based on the "kidney dominates bone" theory of TCM, A. senticosus can strengthen bone and Syringin may be one of the responsibilities. PURPOSE: The objectives of this study were to estimate the osteoporotic activity of Syringin and reveal the possible molecular mechanisms in vivo. METHODS: Sixty female ICR mice were randomly assigned into sham operated group (SHAM, treated with vehicle) and five ovariectomized subgroups (n = 10 each), treated with vehicle as OVX group, estradiol valerate (EV, 1 mg/kg/day) as positive group, and Syringin (10, 20 and 40 mg/kg/day) as low, moderate and high dosage groups. The therapeutic effect of Syringin against osteoporosis was systematically analyzed by determining the bone mineral density (BMD), bone biomechanical properties, bone microarchitecture and serum biochemical parameters, and the molecular mechanism was also evaluated. RESULTS: After three months of orally administrated intervention, Syringin (10, 20 and 40 mg/kg/day) significantly improved the BMD, bone maximum load and trabecular bone microarchitecture in ovariectomized mice, evidenced by the increased bone mineral content, tissue mineral content, tissue mineral density, trabecular thickness and trabecular number, as well as the decreased trabecular separation in OVX mice. Meanwhile, the activities of tartrate-resistant acid phosphatase, deoxypyridinoline and cathepsin K in OVX mice were also inhibited by Syringin, while the increased body weight and decreased uterus weight seemed not influenced by Syringin administration. Concerning the underlying molecular mechanisms, Syringin significantly downregulated the expression of tumor-necrosis factor receptor-associated factor 6 (TRAF6), nuclear factor kappa B (NF-κB) and receptor activator of nuclear factor kappa B ligand (RANKL) proteins levels, upregulated the expression of osteoprotegerin (OPG), phosphoinositide 3-kinase (PI3K) and protein kinase B (AKT) levels, suggesting that Syringin prevented bone lost by TRAF6-mediated inhibition of NF-κB and stimulation of PI3K/AKT, and subsequently increasing the OPG/RANKL ratio and inhibiting the osteoclastogenesis, finally promoting bone formation. CONCLUSIONS: All of the data implied Syringin possessed the potent anti-osteoporosis activity on ovariectomized mice, and the underlying molecular mechanism may be related to the NF-κB and PI3K/AKT signaling pathways.

Rhein protects against cerebral ischemic­/reperfusion­induced oxidative stress and apoptosis in rats.

The present study aimed to investigate the protective effects of rhein on cerebral ischemic/reperfusion (I/R) injury in rats. The present study focused on the effect of rhein on oxidative stress and apoptotic factors, which are considered to serve an important role in the onset of I/R injury. Sprague­Dawley rats were subjected to middle cerebral artery occlusion. Neurological functional scores (NFSs) were evaluated according to the Zea Longa's score criteria and the area of brain infarct was determined by triphenyltetrazolium chloride staining. The morphology of the nerve cells in the cortex was observed following hematoxylin and eosin staining. In addition, levels of oxidative stress were assessed by measuring the levels of superoxide dismutase (SOD), glutathione­peroxidase (GSH­Px), catalase (CAT) and malondialdehyde (MDA). Levels of B­cell lymphoma-2 (Bcl­2), apoptosis regulator Bax (BAX), caspase-9, caspase­3 and cleaved caspase­3 expression were analyzed using western blot analysis. Levels of caspase­9 and caspase­3 mRNA expression were obtained using reverse transcription­quantitative polymerase chain reaction. The results revealed that treatment with 50 or 100 mg/kg rhein significantly improved the NFS and markedly attenuated the area of infarction. Rhein also significantly reduced the content of MDA and significantly increased SOD, GSH­Px and CAT activity. Western blot analysis indicated that rhein significantly decreased the expression of BAX and enhanced the expression of Bcl­2. Compared with the I/R group, levels of caspase­9, caspase­3 and cleaved caspase­3 protein expression were significantly decreased in the rhein treatment groups. Additionally, rhein treatment significantly reduced levels of caspase­9 and caspase­3 mRNA expression. These results suggest that rhein exhibits protective effects during cerebral I/R injury and its underlying mechanism of action may involve the inhibition of oxidative stress and apoptosis.