Combination of Shengmai San and Radix puerariae ameliorates depression-like symptoms in diabetic rats at the nexus of PI3K/BDNF/SYN protein expression.

BACKGROUND: Hyperglycemia is a characteristic feature of diabetes that often results in neuropsychological complications such as depression. Diabetic individuals are more vulnerable to experience depression compared to the normal population. Thus, novel treatment approaches are required to reduce depressive symptoms among diabetic individuals. Traditional Chinese medicines (TCMs) such as Shengmai San (SMS) and Radix puerariae (R) are usually widely used to treat ailments such as neurological complications since ancient time. METHODS: In this study, SMS was combined with R to prepare an R-SMS formulation and screened for their antidepressant activity in diabetic rats. The antidepressant potential of the prepared combination was evaluated behaviorally using open field test, novelty-induced hypophagia, and forced swim test in diabetic rats with biochemical and protein expression (PI3K, BDNF [brain-derived neurotrophic factor], and SYN [presynaptic vesicle protein]) analysis. RESULTS: Diabetic rats (streptozotocin, 45 mg/kg) showed elevated fasting blood glucose (FBG) >12 mM with depressive symptoms throughout the study. Treatment with R-SMS (0.5, 1.5, and 4.5 g/kg) significantly reverted depressive symptoms in diabetic rats as evinced by significantly (p < 0.05) reduced immobility time with an increased tendency to eat food in a novel environment. Treatment with R-SMS also significantly increased the protein expression of PI3K, BDNF, and SYN protein, which play a crucial role in depression. CONCLUSION: This study showed that R-SMS formulation antagonized depressive symptoms in diabetic rats; thus, this formulation might be studied further to develop as an antidepressant.

Effect of Qingyangshen glycosides on social defeat mice model.

ETHNOPHARMACOLOGICAL RELEVANCE: Qingyangshen (Cynanchum otophyllum C.K.Schneid.PI.Wilson.) is the folk medicine of Yunnan which is renowned for its use in the management of neuropsychiatric diseases. The isolated glycosides from Qingyangshen have demonstrated relief in the social defeat stress, however, mechanism of action has not yet been elucidated. AIM OF THE STUDY: This study is aimed to elucidate the effect of Qingyangshen glycosides (QYS) on chronic social defeat stress (CSDS)-induced depression-like symptoms and the related mechanism. MATERIALS AND METHODS: In mice, CSDS model was developed, and the effect of QYS was evaluated by observing the behavioral performance of these mice exposed to tasks related to depression-like activities. Moreover, microscopic pathological examinutesation was also done. Furthermore, the protein expressions related to social defeat stress were also determined to elucidate the possible underlying mechanism. RESULTS: Our results indicated that QYS treatment reversed the CSDS-induced depressive-like behaviors as measured by the increased sucrose preference, open field activity, and social interactions among mice. The reversal of the morphological changes in the hippocampus of the CSDS mice was also noted. Additionally, QYS treatment also upregulated the silent mating type information regulation 2 homolog 1 (SIRT1), peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), fibronectin III domain containing protein 5 (FNDC5), brain-derived neurotrophic factor (BDNF), tropomyosin-related kinase B (TrkB), and mitogen-activated protein kinase (MAPK) proteins. CONCLUSIONS: Our study indicated that QYS had a good anti-social defeat stress effect on CSDS-induced depression in mice, mainly through SIRT1/PGC-1α/FNDC5/BDNF-TrkB signaling pathway activation.

Effect of Xiongmatang Extract on Behavioral and TRPV1-CGRP/CGRP-R Pathway in Rats With Migraine.

Migraine is a complex neurovascular disease, which seriously affects the quality of life in patients. This study aimed to evaluate the effect of Xiongmatang (XMT) extract on rats with migraine induced by inflammatory soup and the underlying mechanisms. First, 1 week after dural catheterization, inflammatory soup was injected through a microsyringe to stimulate the dura of rats for 6 times (12 days), once every 2 days, 10 µL each time, to establish a migraine model. According to pain threshold analysis, behavioral change detection, and pathological analysis, the effects of XMT extract on rats with migraine were evaluated. The positive, mRNA and protein expression of related factors were detected by immunohistochemistry, RT-QPCR, and Western blot analysis to elucidate the underlying mechanism. XMT extract improved the behavioral performance of rats, and improve the pathological changes in the trigeminal nerve in rats. Further experimental results show that XMT extract regulated the expression of migraine-related factors in the trigeminal nerve, manifested as transient receptor potential vanilloid 1 (TRPV1), calcitonin-gene-related peptide (CGRP), calcitonin receptor-like receptor (CRLR), and receptor activity-modifying protein 1 (RAMP1) positive expression, mRNA expression, and protein expression reduction. XMT extract can significantly improved the behavioral performance of rats with migraine, and its mechanism of action might involve regulating the activity of TRPV1-CGRP/CGRP-R pathway.

Carnosic acid ameliorates depressive-like symptoms along with the modulation of FGF9 in the hippocampus of middle carotid artery occlusion-induced Sprague Dawley rats.

The increased survival rate of stroke patients has led to the higher incidences of post-stroke depression. Carnosic acid has the ability to cross blood brain barrier with good neuro-modulatory actions. Recently, inclined level of fibroblast growth factor 9 (FGF9) in the postmortem brain of the depressed patients was noted. Therefore, in the present study, the effect of carnosic acid on post-stroke depression-like behavior, and the expression of FGF9 were evaluated. After 3 weeks of middle carotid artery occlusion in Sprague Dawley rats, carnosic acid (20 and 40 mg/kg) was administered for 2 weeks. Sucrose preference test, forced swimming test, and open field test were performed and hippocampi were analyzed for FGF9 and FGFR-3. In comparison to post-stroke depressed rats, carnosic acid increased the sucrose preference, and reduced the immobility time of the rats by ~2×. The speed and distance-covered were also increased. At 40 mg/kg, FGF9 was reduced by ~3× while FGFR-3/Actin was increased by ~1.5×. Altogether results suggest anti-depressant-like activity of carnosic acid in post-stroke depressed rats with decreased expression of hippocampal FGF9.

Jiawei Shengmai San herbal formula ameliorates diabetic associate cognitive decline by modulating AKT and CREB in rats.

Memory loss is a complication of diabetes which requires new approaches to its treatment. Shengmai San (SMS) is a famous traditional Chinese formula containing Panax ginseng, Ophiopogon japonicas, and Schisandra chinensis, whereas Radix puerariae has many reported pharmacological uses. In this study the combination, as Jiawei SMS (J-SMS) was screened for its ability to reverse diabetes-associated cognitive decline in rats. This was assessed behaviorally in diabetic rats (Streptozotocin, 45 mg/kg), with biochemical and western blot analysis (Akt and CREB). Diabetic rats showed fasting blood glucose (FBG) in the range of 13-15 mM throughout the study. J-SMS (0.5, 1.5, 4.5 g/kg) treatment significantly improved learning and memory deficit among diabetic rats as evidenced by preference for novel object, reduced escape latency and increased number of platform crossings (p < .05) in the NORT and MWM tests. Treatment with J-SMS also significantly improved the histopathological changes in the diabetic brain and increased the protein expression of AKT and CREB, required for proper memory function (p < .01). This study highlighted that J-SMS can reverse reference and working memory deficit among diabetic rats by modulating AKT and CREB proteins activation. Thus, J-SMS formulation might be possible candidate for further development.

Cytotoxic and genotoxic action of Tagetes patula flower methanol extract and patuletin using the Allium test.

Tagetes patula is used to treat cancer patients in alternative healthcare systems. However, its cytotoxic and genotoxic effects have not been reported. Therefore, themethanol extract of T. patula flower, the ethyl acetate fraction, and the pure compound patuletin were evaluatedusing the Allium test.The methanol extract and fraction contained ~3% and ~36% patuletin, respectively, with ~98% purity. The methanol extract caused inhibition of Allium root growth displaying an IC50 value of ~500 µg/mL, while the fraction and patuletin were more potent by ~2 and ~5 times, respectively. The Allium root tips demonstrated a decline in prophase, metaphase, anaphase, and telophase stages with concomitant decrease in percent mitotic index in the methanol extract (~5.64), fraction, and patuletin (~4) as compared to the control (~7.61). However, in only methanol extract-treated root tips, an increase in metaphase stage was noted. In addition, the methanol extract predominantly induced c-type, misaligned, and multipolar chromosomal abnormalities while the fraction and patuletin displayed fragments and sticky chromosomes. The fraction and patuletin also produced micronuclei (~2%). In conclusion, T. patula flower methanol extract and ethyl acetate fraction are cytotoxicand genotoxic, which most likely could be due to the patuletin. Further preclinical and clinical studies are required to justify its clinical use.

Time-dependent impairments in learning and memory in Streptozotocin-induced hyperglycemic rats.

The sedentary lifestyle is responsible for the high prevalence of diabetes which also impairs cognition including learning and memory. Various studies have highlighted the learning and memory impairments in rodent models but data regarding the timeline of their development and their correlation to biochemical parameters are scarce. So, the present study was designed to investigate the type of memory which is more susceptible to hyperglycemia and its correlation with biochemical parameters such as inflammatory cytokines, cAMP response element binding (CREB) and protein kinase B (Akt) activation. Hyperglycemia was induced using streptozotocin (STZ, 45 mg/kg i.p.) and confirmed by measuring fasting blood glucose levels after 1 week of STZ injection. Learning and memory deficits were evaluated using the Novel Object Recognition Test (NORT) and Morris water maze (MWM), and correlated with biochemical parameters (TNF-α, IL-1ß, and dopamine) at 3, 6 and 9 weeks. STZ-injected rats after 3 weeks of injection demonstrated moderate hyperglycemia (blood glucose = 7.99 ± 0.62 mM) with intact learning and reference memory; however, their working memory was impaired in MWM. Severe hyperglycemia (blood glucose = 11.51 ± 0.69 mM) accompanied by impaired short, long, and working memory was evident after 6 weeks whereas learning was intact. After 9 weeks of STZ injection, hyperglycemia was more pronounced (13.69 ± 1.43 mM) and accompanied by a learning deficit in addition to short, long, and working memory impairments. The extent of hyperglycemia either in terms of duration or severity resulted in enhanced inflammation, down-regulation of the level of dopamine, protein expression of AKT and CREB, which possibly affected learning and memory negatively.

In vitro growth inhibition and cytotoxicity of Euphorbia caducifolia against four human cancer cell lines and its phytochemical characterisation.

Several Euphorbia species have been used in folklore as cancer remedies, however, scientific studies on the cytotoxicity (in vitro studies) of Euphorbia caducifolia are lacking. In present study, anticancer potential of E. caducifolia aerial parts ethanol extract and its fractions were evaluated against human lung (NCI-H460), breast (MCF-7), prostate (PC-3) and cervical (HeLa) cancer cell lines, using sulphorhodamine-B in vitro cytotoxicity (in vitro studies) assay. The ethanol extract demonstrated growth inhibitory effect against all aforementioned cancer cell lines with IC50, 19-135 µg/mL and LC50, ~220 µg/mL, and its petroleum ether fraction obtained on bioactivity guided fraction showed highest activity with IC50, 28-70 µg/mL and LC50, 71 µg/mL against NCI-H460 and MCF-7 cell lines. Its phytochemicals were analysed by gas chromatography-mass spectrometry (GC-MS). The present study provides scientific justification for its traditional use against cancer.

In-vitro assessment of cytotoxicity of halloysite nanotubes against HepG2, HCT116 and human peripheral blood lymphocytes.

Halloysite is a clay mineral with chemical similarity to kaolin, a pharmaceutical ingredient. It consists of mainly aluminosilicate nanotubular particles in the size range of ∼ 200-1000 nm. Many studies have tried to empirically explore this novel clay for its potential in drug delivery systems but no work has yet studied its cytotoxicity from the perspective of oral drug delivery system. In this study, the halloysite nanotubes (HNTs) were subjected to size distribution analyses, which reveal more than 50% of nanotubes in the size range of 500 nm and rest mainly in the sub micrometer range. HNTs were then evaluated for in-vitro cytotoxicity against HCT116 (colorectal carcinoma) and HepG2 (hepatocellular carcinoma) cells which represent the earliest entry point and the first accumulating organ, respectively, for nanoparticles en-route to systemic circulation after oral delivery. Moreover, HNTs were tested for their cytogenetic toxicity against human peripheral blood lymphocytes. Both these results collectively indicated that HNTs are generally safe at practical concentrations of excipients for oral dosage forms.