Clinical efficacy of probiotics in the treatment of alcoholic liver disease: a systematic review and meta-analysis.

Objective: Alcoholic liver disease (ALD) is a liver damage disease caused by long-term heavy drinking. Currently, there is no targeted pharmaceutical intervention available for the treatment of this disease. To address this, this paper evaluates the efficacy and safety of probiotic preparation in treating ALD through conducting a meta-analysis, and provides a valuable insight for clinical decision-making. Methods: A systematic search was conducted across databases, including PubMed, Embase, Web of Science, Cochrane Library, CNKI, VIP, Wanfang, and CBM from the inception dates to October 15, 2023, to identify clinical randomized controlled trials on probiotic preparations in the treatment of ALD. After the literature underwent screening, data extraction, and quality assessment, RevMan 5.3 and Stata 14.2 were employed for data analysis and processing. Results: A total of 9 randomized controlled trials fulfilled the inclusion criteria. The results of the meta-analysis showed that probiotic preparation could significantly improve the liver function of patients with alcoholic liver disease compared with the control group. Probiotic intervention led to a significant reduction in the levels of alanine aminotransferase (MD=-13.36,95%CI:-15.80,-10.91;P<0.00001),aspartate aminotransferase (MD=-16.99,95%CI:-20.38,-13.59;P<0.00001),γ-glutamyl transpeptidase (MD=-18.79,95% CI:-28.23,-9.34; P<0.0001). Concurrently, the level of serum albumin (MD=0.19,95% CI:0.02,0.36;P=0.03) was increased. Furthermore, probiotic intervention could also modulate the composition of intestinal flora in patients with alcoholic liver disease, leading to an augmentation in Bifidobacteria and a reduction in Escherichia coli. However, in patients with alcoholic liver disease, probiotic intervention showed no significant effects on total bilirubin (MD=-0.01,95% CI:-0.17,0.15;P=0.91), tumor necrosis factor-α (MD=0.03,95% CI:-0.86,0.92;P=0.94) and interleukin-6 (MD=-5.3,95% CI:-16.04,5.45;P=0.33). Conclusion: The meta-analysis indicates that probiotics can improve liver function in alcoholic liver disease, reduce inflammatory responses, regulate intestinal flora, which have potential value in the treatment of alcoholic liver disease. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023472527.

Nicotine exacerbates diabetic nephropathy through upregulation of Grem1 expression.

BACKGROUND: Diabetic nephropathy (DN) is a major complication of diabetes mellitus. Clinical reports indicate that smoking is a significant risk factor for chronic kidney disease, and the tobacco epidemic exacerbates kidney damage in patients with DN. However, the underlying molecular mechanisms remain unclear. METHOD: In the present study, we used a diabetic mouse model to investigate the molecular mechanisms for nicotine-exacerbated DN. Twelve-week-old female mice were injected with streptozotocin (STZ) to establish a hyperglycemic diabetic model. After four months, the control and hyperglycemic diabetic mice were further divided into four groups (control, nicotine, diabetic mellitus, nicotine + diabetic mellitus) by intraperitoneal injection of nicotine or PBS. After two months, urine and blood were collected for kidney injury assay, and renal tissues were harvested for further molecular assays using RNA-seq analysis, real-time PCR, Western blot, and immunohistochemistry. In vitro studies, we used siRNA to suppress Grem1 expression in human podocytes. Then we treated them with nicotine and high glucose to compare podocyte injury. RESULT: Nicotine administration alone did not cause apparent kidney injury, but it significantly increased hyperglycemia-induced albuminuria, BUN, plasma creatinine, and the kidney tissue mRNA expression of KIM-1 and NGAL. Results from RNA-seq analysis, real-time PCR, Western blot, and immunohistochemistry analysis revealed that, compared to hyperglycemia or nicotine alone, the combination of nicotine treatment and hyperglycemia significantly increased the expression of Grem1 and worsened DN. In vitro experiments, suppression of Grem1 expression attenuated nicotine-exacerbated podocyte injury. CONCLUSION: Grem1 plays a vital role in nicotine-exacerbated DN. Grem1 may be a potential therapeutic target for chronic smokers with DN.

Basing on the machine learning model to analyse the coronary calcification score and the coronary flow reserve score to evaluate the degree of coronary artery stenosis.

AIM: To obtain the coronary artery calcium score (CACS) for each branch in coronary artery computed tomography angiography (CCTA) examination combined with the flow fraction reserve (FFR) of each branch in the coronary artery detected by CT and apply a machine learning model (ML) to analyse and predict the severity of coronary artery stenosis. METHODS: All patients who underwent coronary computed tomography angiography (CCTA) from January 2019 to April 2022 in the HOSPITAL (T.C.M) AFFILIATED TO SOUTHWEST MEDICAL UNIVERSITY) were retrospectively screened, and their sex, age, characteristics of lipid-containing lesions, coronary calcium score (CACS) and CT-FFR values were collected. Five machine learning models, random forest (RF), k-nearest neighbour algorithm (KNN), kernel logistic regression, support vector machine (SVM) and radial basis function neural network (RBFNN), were used as predictive models to evaluate the severity of coronary stenosis. RESULTS: Among the five machine learning models, the SVM model achieved the best prediction performance, and the prediction accuracy of mild stenosis was up to 90%. Second, age and male sex were important influencing factors of increasing CACS and decreasing CT-FFR. Moreover, the critical CACS value of myocardial ischemia >200.70 was calculated. CONCLUSION: Through computer machine learning model analysis, we prove the importance of CACS and FFR in predicting coronary stenosis, especially the prominent vector machine model, which promotes the application of artificial intelligence computer learning methods in the field of medical analysis.

Inositol polyphosphate multikinase IPMK-1 regulates development through IP3/calcium signaling in Caenorhabditis elegans.

Inositol polyphosphate multikinase (IPMK) is a conserved protein that initiates the production of inositol phosphate intracellular messengers and is critical for regulating a variety of cellular processes. Here, we report that the C. elegans IPMK-1, which is homologous to the mammalian inositol polyphosphate multikinase, plays a crucial role in regulating rhythmic behavior and development. The deletion mutant ipmk-1(tm2687) displays a long defecation cycle period and retarded postembryonic growth. The expression of functional ipmk-1::GFP was detected in the pharyngeal muscles, amphid sheath cells, the intestine, excretory (canal) cells, proximal gonad, and spermatheca. The expression of IPMK-1 in the intestine was sufficient for the wild-type phenotype. The IP3-kinase activity of IPMK-1 is required for defecation rhythms and postembryonic development. The defective phenotypes of ipmk-1(tm2687) could be rescued by a loss-of-function mutation in type I inositol 5-phosphatase homolog (IPP-5) and improved by a supplemental Ca2+ in the medium. Our work demonstrates that IPMK-1 and the signaling molecule inositol triphosphate (IP3) pathway modulate rhythmic behaviors and development by dynamically regulating the concentration of intracellular Ca2+ in C. elegans. Advances in understanding the molecular regulation of Ca2+ homeostasis and regulation of organism development may lead to therapeutic strategies that modulate Ca2+ signaling to enhance function and counteract disease processes. Unraveling the physiological role of IPMK and the underlying functional mechanism in C. elegans would contribute to understanding the role of IPMK in other species, especially in mammals, and benefit further research on the involvement of IPMK in disease.

A Dihydroflavonoid Naringin Extends the Lifespan of C. elegans and Delays the Progression of Aging-Related Diseases in PD/AD Models via DAF-16.

Naringin is a dihydroflavonoid, which is rich in several plant species used for herbal medicine. It has a wide range of biological activities, including antineoplastic, anti-inflammatory, antiphotoaging, and antioxidative activities. So it would be interesting to know if naringin has an effect on aging and aging-related diseases. We examined the effect of naringin on the aging of Caenorhabditis elegans (C. elegans). Our results showed that naringin could extend the lifespan of C. elegans. Moreover, naringin could also increase the thermal and oxidative stress tolerance, reduce the accumulation of lipofuscin, and delay the progress of aging-related diseases in C. elegans models of AD and PD. Naringin could not significantly extend the lifespan of long-lived mutants from genes in insulin/IGF-1 signaling (IIS) and nutrient-sensing pathways, such as daf-2, akt-2, akt-1, eat-2, sir-2.1, and rsks-1. Naringin treatment prolonged the lifespan of long-lived glp-1 mutants, which have decreased reproductive stem cells. Naringin could not extend the lifespan of a null mutant of the fox-head transcription factor DAF-16. Moreover, naringin could increase the mRNA expression of genes regulated by daf-16 and itself. In conclusion, we show that a natural product naringin could extend the lifespan of C. elegans and delay the progression of aging-related diseases in C. elegans models via DAF-16.

Secoisolariciresinol Diglucoside Delays the Progression of Aging-Related Diseases and Extends the Lifespan of Caenorhabditis elegans via DAF-16 and HSF-1.

Secoisolariciresinol diglucoside (SDG) is a phytoestrogen and rich in food flaxseed, sunflower seeds, and sesame seeds. Among the beneficial pharmacological activities of SDG on health, many are age related, such as anticancer, antidiabetes, antioxidant, and neuroprotective effects. Thus, we investigated if SDG had an effect on antiaging in Caenorhabditis elegans (C. elegans). Our results showed that SDG could extend the lifespan of C. elegans by up to 22.0%, delay age-related decline of body movement, reduce the lethality of heat and oxidative stress, alleviate dopamine neurodegeneration induced by 6-hydroxydopamine (6-OHDA), and decrease the toxicity of Aß protein in C. elegans. SDG could increase the expression of the downstream genes of DAF-16, DAF-12, NHR-80, and HSF-1 at mRNA level. SDG could not extend the lifespan of mutants from genes daf-16, hsf-1, nhr-80, daf-12, glp-1, eat-2, and aak-2. The above results suggested that SDG might enhance the stress resistance, delay the progression of aging-related diseases, and extend the lifespan of C. elegans via DAF-16 and HSF-1.

Tectochrysin increases stress resistance and extends the lifespan of Caenorhabditis elegans via FOXO/DAF-16.

Aging is related to the lowered overall functioning and increased risk for various age-related diseases in humans. Tectochrysin is a flavonoid compound and rich in a traditional Chinese Medicine Alpinia oxyphylla Miq., which has antioxidant, anti-inflammatory, anti-cancer, anti-bacterial, anti-diarrhea, hepatoprotective, and neuro-protective effects. Therefore, we tested if tectochrysin had an effect on aging in Caenorhabditis elegans (C. elegans). Our results showed that tectochrysin could extend the lifespan of C. elegans by up to 21.0%, delay the age-related decline of body movement, improve high temperature-stress resistance and anti-infection capacity, and protected worms against Aß1-42-induced toxicity. Tectochrysin could not extend the lifespan of the mutants from genes daf-2, daf-16, eat-2, aak-2, skn-1, and hsf-1. Tectochrysin could increase the expression of DAF-16 regulated genes. The extension of lifespan by tectochrysin requires FOXO/DAF-16 and HSF-1. Overall, our findings suggest that tectochrysin may have a potential effect on extending lifespan and age-related diseases.

EDA2R mediates podocyte injury in high glucose milieu.

EDA2R is a member of the large family of tumor necrosis factor receptor (TNFR). Previous studies suggested that EDA2R expression might be increased in the kidneys of diabetic mice. However, its mRNA and protein expression in kidneys were not analyzed; moreover, its role in the development of diabetic kidney disease was not explored. Here we analyzed the mRNA and protein expressions of EDA2R in diabetic kidneys and examined its role in the podocyte injury in high glucose milieu. By analysis with real-time PCR, Western blotting, we found that both the mRNA and protein levels of EDA2R were increased in the kidneys of diabetic mice. Immunohistochemical studies revealed that EDA2R expression was enhanced in both glomerular and tubular cells of diabetic mice and humans. In vitro studies, high glucose increased EDA2R expression in cultured human podocytes. Overexpression of EDA2R in podocytes promoted podocyte apoptosis and decreased nephrin expression. Moreover, ED2AR increased ROS generation in podocytes, while inhibiting ROS generation attenuates EDA2R-mediated podocyte injury. In addition, EDA2R silencing partially suppressed high glucose-induced ROS generation, apoptosis, and nephrin decrease. Our study demonstrated that high glucose increases EDA2R expression in kidney cells and that EDA2R induces podocyte apoptosis and dedifferentiation in high glucose milieu partially through enhanced ROS generation.

Prophylactic Effects of Bifidobacterium adolescentis on Anxiety and Depression-Like Phenotypes After Chronic Stress: A Role of the Gut Microbiota-Inflammation Axis.

Stress disturbs the balance of the gut microbiota and stimulates inflammation-to-brain mechanisms. Moreover, stress leads to anxiety and depressive disorders. Bifidobacterium adolescentis displays distinct anti-inflammatory effects. However, no report has focused on the anxiolytic and antidepressant effects of B. adolescentis related to the gut microbiome and the inflammation on chronic restraint stress (CRS) in mice. We found that pretreatment with B. adolescentis increased the time spent in the center of the open field apparatus, increased the percentage of entries into the open arms of the elevated plus-maze (EPM) and the percentage of time spent in the open arms of the EPM, and decreased the immobility duration in the tail suspension test as well as the forced swimming test (FST). Moreover, B. adolescentis increased the sequence proportion of Lactobacillus and reduced the sequence proportion of Bacteroides in feces. Furthermore, B. adolescentis markedly reduced the protein expression of interleukin-1ß (IL-1ß), tumor necrosis factor α (TNF-α), p-nuclear factor-kappa B (NF-κB) p65 and Iba1 and elevated brain derived neurotrophic factor (BDNF) expression in the hippocampus. We conclude that the anxiolytic and antidepressant effects of B. adolescentis are related to reducing inflammatory cytokines and rebalancing the gut microbiota.

Pyrazolo[1,5-a]pyrimidine TRPC6 antagonists for the treatment of gastric cancer.

Transient receptor potential canonical 6 (TRPC6) proteins form receptor-operated Ca2+-permeable channels, which have been thought to bring benefit to the treatment of diseases, including cancer. However, selective antagonists for TRPC channels are rare and none of them has been tested against gastric cancer. Compound 14a and analogs were synthesized by chemical elaboration of previously reported TRPC3/6/7 agonist 4o. 14a had very weak agonist activity at TRPC6 expressed in HEK293 cells but exhibited strong inhibition on both 4o-mediated and receptor-operated activation of TRPC6 with an IC50 of about 1 µM. When applied to the culture media, 14a suppressed proliferation of AGS and MKN45 cells with IC50 values of 17.1 ±â€¯0.3 and 18.5 ±â€¯1.0 µM, respectively, and inhibited tube formation and migration of cultured human endothelial cells. This anti-tumor effect on gastric cancer was further verified in xenograft models using nude mice. This study has found a new tool compound which shows excellent therapeutic potential against human gastric cancer most likely through targeting TRPC6 channels.

Nicotine enhances mesangial cell proliferation and fibronectin production in high glucose milieu via activation of Wnt/ß-catenin pathway.

Diabetic nephropathy (DN) is a major complication of diabetes mellitus. Clinic reports indicate cigarette smoking is an independent risk factor for chronic kidney disease including DN; however, the underlying molecular mechanisms are not clear. Recent studies have demonstrated that nicotine, one of the active compounds in cigarette smoke, contributes to the pathogenesis of the cigarette smoking-accelerated chronic kidney disease. One of the characteristics of DN is the expansion of mesangium, a precursor of glomerular sclerosis. In the present study, we examined the involvement of Wnt/ß-catenin pathway in nicotine-mediated mesangial cell growth in high glucose milieu. Primary human renal mesangial cells were treated with nicotine in the presence of normal (5 mM) or high glucose (30 mM) followed by evaluation for cell growth. In the presence of normal glucose, nicotine increased both the total cell numbers and Ki-67 positive cell ratio, indicating that nicotine stimulated mesangial cell proliferation. Although high glucose itself also stimulated mesangial cell proliferation, nicotine further enhanced the mitogenic effect of high glucose. Similarly, nicotine increased the expression of Wnts, ß-catenin, and fibronectin in normal glucose medium, but further increased mesangial cell expression of these proteins in high glucose milieu. Pharmacological inhibition or genetic knockdown of ß-catenin activity or expression with specific inhibitor FH535 or siRNA significantly impaired the nicotine/glucose-stimulated cell proliferation and fibronectin production. We conclude that nicotine may enhance renal mesangial cell proliferation and fibronectin production under high glucose milieus partly through activating Wnt/ß-catenin pathway. Our study provides insight into molecular mechanisms involved in DN.

Pyrazolopyrimidines as Potent Stimulators for Transient Receptor Potential Canonical 3/6/7 Channels.

Transient receptor potential canonical 3/6/7 (TRPC3/6/7) are highly homologous receptor-operated nonselective cation channels. Despite their physiological significance, very few selective and potent agonists are available for functional examination of these channels. Using a cell-based high throughput screening approach, a lead compound with the pyrazolopyrimidine skeleton was identified as a TRPC6 agonist. Synthetic schemes for the lead and its analogues were established, and structural-activity relationship studies were carried out. A series of potent and direct agonists of TRPC3/6/7 channels were identified, and among them, 4m-4p have a potency order of TRPC3 > C7 > C6, with 4n being the most potent with an EC50 of <20 nM on TRPC3. Importantly, these compounds exhibited no stimulatory activity on related TRP channels. The potent and selective compounds described here should be suitable for evaluation of the roles of TRPC channels in the physiology and pathogenesis of diseases, including glomerulosclerosis and cancer.

Chlorogenic Acid Extends the Lifespan of Caenorhabditis elegans via Insulin/IGF-1 Signaling Pathway.

Coffee and tea, two of the most popular drinks around the world, share many in common from chemical components to beneficial effects on human health. One of their shared components, the polyphenols, most notably chlorogenic acid (CGA), was supposed to account for many of the beneficial effects on ameliorating diseases occurred accompanying people aging, such as the antioxidant effect and against diabetes and cardiovascular disease. CGA is also present in many traditional Chinese medicines. However, the mechanism of these effects was vague. The aging signaling pathways were conservative from yeast and worms to mammals. So, we tested if CGA had an effect on aging in Caenorhabditis elegans. We found that CGA could extend the lifespan of C. elegans by up to 20.1%, delay the age-related decline of body movement, and improve stress resistance. We conducted genetic analysis with a series of worm mutants and found that CGA could extend the lifespan of the mutants of eat-2, glp-1, and isp-1, but not of daf-2, pdk-1, akt-1, akt-2, sgk-1, and clk-1. CGA could activate the FOXO transcription factors DAF-16, HSF-1, SKN-1, and HIF-1, but not SIR-2.1. Taken together, CGA might extend the lifespan of C. elegans mainly via DAF-16 in insulin/IGF-1 signaling pathway.

Volvalerine A, an unprecedented N-containing sesquiterpenoid dimer derivative from Valeriana officinalis var. latifolia.

Volvalerine A (1), a novel N-containing bisesquiterpenoid derivative with a dihydroisoxazole ring, and its possible biosynthetic precursor, 1-hydroxy-1,11,11-trimethyldecahydrocyclopropane azulene-10-one (2), were isolated from the roots of Valeriana officinalis var. latifolia. Their structures and relative configurations were identified using spectroscopic data and X-ray crystallography. A plausible biosynthetic pathway for 1 is also presented.

Iridoids and sesquiterpenoids of Valeriana stenoptera and their effects on NGF-induced neurite outgrowth in PC12 cells.

Twenty-one compounds (nine iridoids and twelve sesquiterpenoids), including ten previously unknown (five iridoids and five sesquiterpenoids) were isolated from whole dried material of Valeriana stenoptera. Structures were established on the basis of extensive spectroscopic analysis and the relative stereochemistry of 13-hydroxypatchoulol A was further confirmed by X-ray crystallographic data. All isolates were evaluated for their effects on nerve growth factor (NGF)-mediated neurite outgrowth in pheochromocytoma (PC12) cells and seven compounds showed potent promoting effects.

Acute Treatment with a Novel TRPC4/C5 Channel Inhibitor Produces Antidepressant and Anxiolytic-Like Effects in Mice.

Transient receptor potential canonical (TRPC) channels are widely expressed in brain and involved in various aspects of brain function. Both TRPC4 and TRPC5 have been implicated in innate fear function, which represents a key response to environmental stress. However, to what extent the TRPC4/C5 channels are involved in psychiatric disorders remains unexplored. Here, we tested the antidepressant and anxiolytic-like effects of a newly identified TRPC4/C5 inhibitor, M084. We show that a single intraperitoneal administration of M084 at 10 mg/kg body weight to C57BL/6 male mice significantly shortened the immobility time in forced swim test and tail suspension test within as short as 2 hours. The M084-treated mice spent more time exploring in illuminated and open areas in light/dark transition test and elevated plus maze test. In mice subjected to chronic unpredictable stress, M084 treatment reversed the enhanced immobility time in forced swim test and decreased the latency to feed in novelty suppressed feeding test. The treatment of M084 increased BDNF expression in both mRNA and protein levels, as well as phosphorylation levels of AKT and ERK, in prefrontal cortex. Our results indicate that M084 exerts rapid antidepressant and anxiolytic-like effects at least in part by acting on BDNF and its downstream signaling. We propose M084 as a lead compound for further druggability research.

Triterpenoids with Promoting Effects on the Differentiation of PC12 Cells from the Steamed Roots of Panax notoginseng.

The roots of Panax notoginseng, an important Chinese medicinal plant, have been used traditionally in both the raw and processed forms, due to the different chemical constituents and bioactivities found. Thirty-eight dammarane-type triterpenoid saponins were isolated from the steam-processed roots of P. notoginseng, including 18 new substances, namely, notoginsenosides SP1-SP18 (1-18). The structures of 1-18 were determined on the basis of spectroscopic analysis and acidic hydrolysis. The absolute configuration of the hydroxy group at C-24 in 1-4, 19, and 20 was determined in each case by Mo2(AcO)4-induced circular dichroism. The new compounds were found to feature a diversity of highly oxygenated side chains, formed by hydrolysis of the C-20 sugar moiety followed by dehydration, dehydrogenation, epoxidation, hydroxylation, or methoxylation of the main saponins in the raw roots. The new saponins 1, 2, 6-8, 14, and 17 and the known compounds 20-27 showed promoting effects on the differentiation of PC12 cells, at a concentration of 10 µM.

Minor dehydrogenated and cleavaged dammarane-type saponins from the steamed roots of Panax notoginseng.

Nine new minor dehydrogenated and cleavaged dammarane-type triterpenoid saponins, namely notoginsenosides ST6-ST14 (1-9) were isolated from the steamed roots of Panax notoginseng, together with 14 known ones. Among them, 5-7 and 21-22 were protopanaxadiol type and the left 18 compounds, including 1-4, 8-20, and 23 were protopanaxatriol type saponins. Their structures were identified by extensive analysis of MS, 1D and 2D NMR spectra, and acidic hydrolysis. Resulted from the side chain cleavage, the new saponins 1 and 2 featured in a ketone group at C-25, and 3-5 had an aldehyde unit at C-23. The known saponins 12, 16 and 18 displayed the enhancing potential of neurite outgrowth of NGF-mediated PC12 cells at a concentration of 10 µM, while 20 exhibited acetyl cholinesterase inhibitory activity, with IC50 value of 13.97 µM.

Effect of nigranoic acid on Ca²âº influx and its downstream signal mechanism in NGF-differentiated PC12 cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Schisandra chinensis has a long history of use as a famous traditional Chinese medicine. The plants of genus Schisandra, especially Schisandra neglecta, Schisandra rubriflora, and Schisandra sphaerandra are used in the same way as Schisandra chinensis in the folk medicine to treat insomnia, fatigue, increasing intelligence, and tranquilizing. Many studies showed that lignans were the major active components of Schisandra genus, whereas the bioactivity of abundant triterpenoids in Schisandra genus, such as nigranoic acid (SBB1, 3,4-secocycloartene triterpenoid), has not been examined yet in neuropathology. MATERIALS AND METHODS: After treating with SBB1, intracellular Ca(2+) concentration was analyzed by Ca(2+) fluorescent indicator (Fluo-4 AM) in NGF-differentiated PC12 cells. Intracellular nitric oxide (NO) level was analyzed using NO fluorescent indicator (DAF-FM). The expression of extracellular signal regulated kinase 1 and 2 (ERK1/2) was analyzed by western blotting, and the temporal mRNA for BDNF and c-fos was analyzed using reverse transcription quantitative PCR. RESULT: We found that SBB1 induced Ca(2+) influx in a time- and concentration-dependent manner, which was significantly attenuated in Ca(2+) free media. SBB1 promoted the intracellular NO production which depended on increasing cytoplasmic Ca(2+) level. Moreover, SBB1 stimulated activation of ERK1/2 through Ca(2+)-CaMKII pathway. In addition, we found that SBB1 increased the expression of BDNF and c-fos mRNA. CONCLUSION: These results suggest that SBB1 is able to promote NO production and stimulate phosphorylation of ERK1/2 through Ca(2+) influx, further impact expression of BDNF and c-fos, which provides evidence for the effects of SBB1 that may be benefit to enhance mental and intellectual functions.