Bacterial, short-chain fatty acid and gas profiles of partially hydrolyzed guar gum in vitro fermentation by human fecal microbiota.

Carbohydrates with different structures have metabolic differences in the human body, as well as individual differences. The present study aimed to investigate the effects of bacterial, short-chain fatty acids (SCFAs) and gas profiles of partially hydrolyzed guar gum (PHGG) on the fecal microbiota of 41 Chinese individuals by simulated fermentation in vitro. Results showed that PHGG stimulated the growth of Bifidobacterium and Faecalibacterium, inhibited the growth of Escherichia-Shigella, Klebsiella, and Dorea, and induced the production of fermentation gases (CO2, and H2) and SCFAs (acetic acid, butyric acid). Furthermore, Bifidobacterium was significantly increased in the young female and the old male-originated samples, while Klebsiella was significantly decreased in the old female ones after PHGG intervention, and there were also certain differences in gases and SCFAs among different population samples. These findings indicate that PHGG can modulate gut microbiota and metabolism well, whereas its use varies in different populations.

HPC Framework for Performing in Silico Trials Using a 3D Virtual Human Cardiac Population as Means to Assess Drug-Induced Arrhythmic Risk.

Following the 3 R's principles of animal research-replacement, reduction, and refinement-a high-performance computational framework was produced to generate a platform to perform human cardiac in-silico clinical trials as means to assess the pro-arrhythmic risk after the administrations of one or combination of two potentially arrhythmic drugs. The drugs assessed in this study were hydroxychloroquine and azithromycin. The framework employs electrophysiology simulations on high-resolution three-dimensional, biventricular human heart anatomies including phenotypic variabilities, so as to determine if differential QT-prolongation responds to drugs as observed clinically. These simulations also reproduce sex-specific ionic channel characteristics. The derived changes in the pseudo-electrocardiograms, calcium concentrations, as well as activation patterns within 3D geometries were evaluated for signs of induced arrhythmia. The virtual subjects could be evaluated at two different cycle lengths: at a normal heart rate and at a heart rate associated with stress as means to analyze the proarrhythmic risks after the administrations of hydroxychloroquine and azithromycin. Additionally, a series of experiments performed on reanimated swine hearts utilizing Visible Heart® methodologies in a four-chamber working heart model were performed to verify the arrhythmic behaviors observed in the in silico trials.The obtained results indicated similar pro-arrhythmic risk assessments within the virtual population as compared to published clinical trials (21% clinical risk vs 21.8% in silico trial risk). Evidence of transmurally heterogeneous action potential prolongations after providing a large dose of hydroxychloroquine was found as the observed mechanisms for elicited arrhythmias, both in the in vitro and the in silico models. The proposed workflow for in silico clinical drug cardiotoxicity trials allows for reproducing the complex behavior of cardiac electrophysiology in a varied population, in a matter of a few days as compared to the months or years it requires for most in vivo human clinical trials. Importantly, our results provided evidence of the common phenotype variants that produce distinct drug-induced arrhythmogenic outcomes.

Icariin improves learning and memory function in Aß1-42-induced AD mice through regulation of the BDNF-TrκB signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Epimedium brevicornu Maxim. is a traditional medicinal Chinese herb that is enriched with flavonoids, which have remarkably high medicinal value. Icariin (ICA) is a marker compound isolated from the total flavonoids of Epimedium brevicornu Maxim. It has been shown to improve Neurodegenerative disease, therefore, ICA is probably a potential drug for treating AD. MATERIALS AND METHODS: The 6-8-week-old SPF-class male ICR mice were randomly divided into 8 groups for modeling, and then the mice were administered orally with ICA for 21 days. The behavioral experiments were conducted to evaluate if learning and memory behavior were absent in mice, confirming that infusion of Amyloid ß-protein (Aß)1-42 caused significant memory impairment. The morphological changes and damage of neurons in the mice's brains were observed by HE and Nissl staining. The spinous protrusions (dendritic spines) on neuronal dendrites were investigated by Golgi-Cox staining. The molecular mechanism of ICA was examined by Western Blot. The protein docking of ICA and Donepezil with BDNF were analyzed to determine their interaction. RESULTS: The behavioral experimental results showed that in Aß1-42-induced AD mice, the learning and memory abilities were improved after using ICA. At the same time, the low, medium, and high doses of ICA could reduce the content of Aß1-42 in the hippocampus of AD mice, repair neuronal damage, enhance synaptic plasticity, as well as increase the expression of BDNF, TrκB, CREB, Akt, GAP43, PSD95, and SYN proteins in the hippocampus of mice. However, the effect with high doses of ICA is more pronounced. The high-dose administration of ICA has the best therapeutic effect on AD mice. After administering the inhibitor k252a, the therapeutic effect of ICA was reversed. The macromolecular docking results of ICA and BDNF protein demonstrated a strong interaction of -7.8 kcal/mol, which indicates that ICA plays a therapeutic role in AD mice by regulating the BDNF-TrκB signaling pathway. CONCLUSIONS: The results confirm that ICA can repair neuronal damage, enhance synaptic plasticity, as well as ultimately improve learning and memory impairment through the regulation of the BDNF-TrκB signaling pathway.

Extraction optimization and constituent analysis of total flavonoid from Hosta plantaginea (Lam.) Aschers flowers and its ameliorative effect on chronic prostatitis via inhibition of multiple inflammatory pathways in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Hosta plantaginea (Lam.) Aschers flowers (HPF) are well-known for their high flavonoid content, which contribute to their widely as traditional Chinese medicine for alleviating inflammation. Despite their recognized potential, information regarding the total flavonoid (TF) of HPF and its therapeutic application in treating chronic prostatitis (CP) remains unknown. AIM OF THE STUDY: We aimed to investigate the extraction optimization, constituent analysis, and alleviating effect of TF on CP as well as its potential mechanism. MATERIALS AND METHODS: The optimized extraction of TF from HPF was explored using response surface methodology with a Box-Behnken design model. The major flavonoids in TF were identified based on UHPLC-MS approach. Efficacy of TF (25 and 100 mg/kg, p.o.) on CP was evaluated in prostate antigen emulsion-induced autoimmune CP rat model by measuring prostatic index, the levels of leukocytes and lecithin bodies, as well as histopathological examination. The protein expression contents were detected by western blotting. Additionally, the antioxidant (DPPH and ABTS) and anti-inflammatory (cyclooxygenase 2, COX-2 inhibitory) effects of TF were also evaluated in vitro. RESULTS: The optimized conditions for TF extraction were determined as 60% ethanol concentration, 30 mL/g liquid-to-solid ratio, 30 min extraction time, and 90 °C extraction temperature, and the extraction ratio is 65.98 ± 2.14%. A total of 15 major flavonoids in TF were characterized by comparison with reference standards. TF ameliorated the efficacy of CP in rats in a dose-independent manner, including reduced prostatic index and leukocytes levels, elevated lecithin body levels, ameliorated histopathological damage to prostate, and suppressed phosphorylated protein expressions of nuclear factor kappa-B (NF-κB) p65, inhibitor of NF-κB alpha (IκBα), c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (Erk), just another kinase 1 (JAK1), signal transducer and activator of transcription 3 (STAT3), phosphoinositide 3-kinase (PI3K) and protein kinase B (Akt). Simultaneously, the IC50 of TF to DPPH, ABTS radicals, and COX-2 were 2.02, 1.79, and 0.0838 mg/mL, respectively. CONCLUSIONS: We first demonstrated that TF from HPF represents a promising candidate to alleviate CP through suppression of NF-κB, MAPKs, JAK-STAT, and PI3K-Akt signaling pathways.

Traditional Chinese Medicine formula Wubi Shanyao Pills protects against reproductive aging by activating SIRT1/3 to reduce apoptosis.

ETHNOPHARMACOLOGICAL RELEVANCE: The study of male reproductive aging and its associated concerns holds significant importance within the realm of health issues affecting the elderly population. Wubi Shanyao Pills (WSP), a traditional Chinese patent medicine originating from the Tang Dynasty, has been recognized for its ability to enhance male sexual functions while also tonifying the kidney and spleen. Nevertheless, the precise effects and underlying mechanisms through which WSP ameliorates the decline in reproductive function among aging men remain uncertain. AIM OF THE STUDY: This study elucidated the distinctive impacts of WSP on ameliorating the decline in reproductive function caused by natural aging, as well as its underlying mechanisms. MATERIALS AND METHODS: Initially, male mice at the age of 15 months were administered WSP orally at doses of 0.375, 0.75, and 1.50 g/kg per day for a duration of 8 consecutive weeks. The impact of WSP on age-related manifestations in naturally aging mice was assessed based on their behavioral performance. The renal function of the mice was evaluated by measuring serum biochemical indicators, including Creatinine (CR), Uric acid (UA), and Blood urea nitrogen (BUN). Additionally, Superoxide dismutase (SOD) and Malonaldehyde (MDA) levels in renal tissue were determined using applied chemistry methods. Then assessed the levels of Nitric oxide (NO), Total nitric oxide synthase (T-NOS), Guanosine cyclase (GC), and Cyclic guanosine monophosphate (cGMP) in the penile tissue, as well as the expression of Endothelial nitric oxide synthase (eNOS) and Guanylate Cyclase Activator (GUCA) protein, in order to investigate the erectile function of the penis. Additionally, the quality of epididymal sperm was examined using an electron microscope. Furthermore, the serum sex hormone level and related protein expression were determined through the utilization of enzyme-linked immunosorbent assay and immunohistochemistry techniques. Pathological alterations and the ultrastructure of the testis were investigated using hematoxylin-eosin staining and transmission electron microscopy. Subsequently, the apoptosis of spermatogenic cells in the testes was assessed employing TUNEL, immunofluorescence, western blotting, and quantitative real-time polymerase chain reaction. RESULTS: The administration of WSP has been found to enhance the behavioral performance and sexual behavior in aged mice. It's also could increase in serum levels of CR, UA, and BUN, as well as the elevation of SOD activity in kidney tissue, which subsequently leads to a reduction in MDA levels and an improvement in the structural damage caused by aging in the kidney tissue. Consequently, the renal function is enhanced. Additionally, WSP has been observed to elevate the levels of NO, T-NOS, GC, and cGMP in penile tissue, along with an increase in eNOS and GUCA protein expression, indicating an improvement in penile erectile function. The administration of WSP resulted in a decrease in the occurrence of programmed cell death in testicular germ cells, leading to an enhancement in sperm quality and the overall function of testicular spermatogenesis. This improvement can be attributed to the modulation of hormone levels and the regulation of SIRT1/3, p53, FOXO3, Bax, and Caspase-3 expression. CONCLUSION: Collectively, our findings indicate that the administration of WSP has the potential to impede the occurrence of programmed cell death in testicular cells by modulating the expression of SIRT1/3 and subsequent genes associated with apoptosis. Consequently, this regulatory mechanism facilitates the proliferation of testicular cells and sustains the spermatogenic function of the testes. Consequently, by modulating the levels of sexual hormones in naturally aging mice, WSP ultimately enhances the quality of sperm and reproductive function. Concurrently, it also ameliorates age-related behavioral changes, renal function, and erectile function.

Ginkgolide B attenuates cerebral ischemia-reperfusion injury via inhibition of ferroptosis through disrupting NCOA4-FTH1 interaction.

ETHNOPHARMACOLOGICAL RELEVANCE: Cerebral ischemia/reperfusion (I/R) injury is a major cause of neuronal damage and death. Ginkgolide B (GB) has been shown to exhibit neuroprotective effects in various brain injury models. AIM OF STUDY: The aim of study was to investigate the potential role of GB in protecting against cerebral I/R injury and explore the underlying mechanisms. MATERIALS AND METHODS: Adult male Sprague-Dawley rats were exposed to transient middle cerebral artery occlusion (tMCAO) followed by reperfusion in order to trigger cerebral I/R injury. The rats were treated with different doses of GB, vehicle control or positive drug. Neurological function, infarct volume, and levels of ferroptosis markers were evaluated. In vitro experiments were performed using OGD/R-induced PC12 cells to further investigate the effects of GB on ferroptosis and its mechanisms. In addition, molecular docking, and microscale thermophoresis (MST) assay were conducted to explore the combination of GB and NCOA4. RESULTS: Reduced infarct volume and enhanced neurological function were signs of dose-dependent protection from cerebral I/R injury by GB therapy. Additionally, GB treatment had an impact on the levels of oxidative stress and ferroptosis markers, including reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), and Fe2+ in the cerebral environment during IR injury. Moreover, relevant ferroptosis key factors such as ACSL4, GPX4, FTH1, and NCOA4 can be regulated by GB. In OGD/R-induced PC12 cells, GB protected against ferroptosis by inhibiting autophagy and disrupting the interaction of NCOA4-FTH1. CONCLUSION: Our findings suggest that GB may protect against cerebral I/R injury by inhibiting ferroptosis through disrupting NCOA4-FTH1 interaction. GB has potential therapeutic applications for cerebral I/R injury, and further investigation of the underlying mechanisms and clinical trials are warranted.

Withania somnifera ameliorates sexual arousal and impotence in stressed sexually sluggish male rats by modulating neurotransmitters and NO/cGMP/PDE5α pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Psychological stress is a growing global threat to male sexual potency and erection efficiency. Withania somnifera (L.) Dunal (WS), also known as Ashwagandha, is a well-known Ayurvedic herb. The roots of Withania somnifera improve the body's ability to handle stress, strengthen the immune system, promote healthy ageing, and have aphrodisiac properties with male sexual stimulation effects. Despite its widespread acceptance as an Ayurvedic stress-relieving drug with beneficial effects on male reproductive health, Withania somnifera has yet to be studied for its potential role in improving the sexual arousal and erectile dysfunction of psychologically stressed sexually sluggish males. AIM OF THE STUDY: To investigate the therapeutic effects of purified root powder of Withania somnifera on sexual behaviour and erectile efficiency in stressed sexually sluggish male rats. MATERIALS AND METHODS: Sexually sluggish male rats were screened by premating tests after being exposed to a psychological stressor, restraint stress, 3 h/day for 30 days. Subsequently, these rats were treated with purified root powder of WS (150 or 300 mg/kg/day-PO) or sildenafil (5 mg/kg/day-PO) for 30 days. The rats were sacrificed after 24 h of the last treatment, and the effects on various factors related to sexual behaviour, penile histomorphology, serum hormones, and neurotransmitters associated with sexual arousal and penile erection were examined. RESULTS: WS treatment improves prosexual and sexual behaviour in psychologically stressed sexually sluggish male rats by increasing non-contact erections and mounts, intromission, and ejaculation frequencies, while decreasing sexual exhaustion by decreasing post-ejaculation intervals and latencies. WS also modulates neurotransmitters and hormones associated with sexual desire and stress, including dopamine, serotonin, corticosterone, and prolactin. Additionally, there was also a dose-dependent increase in serum LH, FSH, and testosterone levels. The administration of WS to sexually sluggish rats resulted in significant improvements in penile histomorphology, specifically by increasing the ratio of smooth muscle (SM) to collagen. Furthermore, in sexually sluggish rats, WS treatment increased the expression of markers associated with penile erection facilitation, such as nNOS, eNOS, p-Akt, nitric oxide, acetylcholine, and cGMP. Notably, WS treatment decreased the expression of penile PDE5α in these rats in a dose-dependent manner. Remarkably, the therapeutic effects of WS are comparable to those of sildenafil. CONCLUSIONS: Purified root powder of Withania somnifera was found to improve sexual arousal and erection efficiency in stressed, sexually sluggish male rats. This improvement was achieved by modulating the HPG and HPA axes as well as the NO/cGMP/PDE5α pathway involved in penile erection. Thus, our findings strongly support the potent therapeutic potential of purified root powder of WS in improving the sexual health of stressed sexually sluggish rats.

Gastroprotective effect of eupatilin, a polymethoxyflavone from Artemisia argyi H.Lév. & Vaniot, in ethanol-induced gastric mucosal injury via NF-κB signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Artemisia argyi H.Lév. & Vaniot (AA) has been extensively utilized as an important medicine and food homology in China, Japan, Korea, and eastern parts of Russia, owing to its pharmacological effects, which include anti-inflammatory, antibacterial, antitussive, and antiallergic properties. Despite the extract of AA can significantly alleviate gastric mucosal injury, its precise material basis for effectiveness is not yet clear. As one of the polymethoxy flavonoids with high content in AA, the gastroprotective activity and molecular mechanism of eupatilin (EUP) require further investigation. AIM OF THE STUDY: This study aims to investigate the gastroprotective effects and possible mechanisms of EUP by using an ethanol-induced gastric mucosal injury model in rats. MATERIALS AND METHODS: EUP was isolated from 95% ethanol extract of AA using a systematic phytochemical method. The gastroprotective activity of EUP was evaluated using a male SD rat model with ethanol-induced gastric mucosa injury. Histopathology evaluation of gastric tissues was performed using hematoxylin and eosin (H&E) staining. The levels of cytokines in the plasma and tissues were tested using the ELISA kits, while western blot analysis was employed to assess the expressions of COX-2, iNOS, and NF-κB pathway proteins. RESULTS: A sufficient amount of EUP was obtained from AA through chromatographic methods and identified by NMR experiment. In vivo, experimental results proved that EUP could significantly alleviate pathological features, increased SOD, GSH, and IL-10 levels, and decreased the contents of MDA, TNF-α, IL-1ß, and IL-6. Further in vitro and in vivo Western blot experimental results showed that EUP significantly down-regulates the expressions of the NF-κB signal pathway to relieve inflammatory responses. CONCLUSION: This study demonstrated that EUP could exert gastroprotective effects by inhibiting inflammation, enhancing gastric mucosal defense, and ameliorating oxidative stress, which is beneficial for providing scientific data for the development of gastric protection.

A blend of Withania somnifera (L.) Dunal root and Abelmoschus esculentus (L.) Moench fruit extracts relieves constipation and improves bowel function: A proof-of-concept clinical investigation.

ETHNOPHARMACOLOGICAL RELEVANCE: Withania somnifera (L.) Dunal (WS) and Abelmoschus esculentus (L.) Moench (AE) are known as Ashwagandha and Okra, respectively, important herbs in traditional medicine for their diverse therapeutic values. WS root is an adaptogen that relieves stress and anxiety and promotes sleep. AE fruit or Okra is widely consumed as a vegetable and is traditionally used to treat diabetes, gastric irritations, ulcers, and obesity. AIM OF THE STUDY: The present randomized, double-blind, placebo-controlled study aimed to establish a proof-of-concept evaluating the efficacy and tolerability of a proprietary blend of standardized extracts of WS root and AE fruit, CL18100F4 in relieving constipation and improving quality of life in adults. MATERIALS AND METHODS: Forty-eight male and female participants (age: 25-60 years) with functional constipation (following Rome-III criteria) were randomized into placebo, 300 or 500 mg of CL18100F4 groups, and supplemented for fourteen consecutive days. RESULTS: CL18100F4 supplementation significantly (p < 0.0001) reduced the Patient Assessment of Constipation-Symptoms (PAC-SYM), Patient Assessment of Constipation-Quality of Life (PAC-QOL), and Gastrointestinal Symptom Rating Scale (GSRS) scores. CL18100F4 supplementation improved sleep quality and reduced stress (p < 0.0001). At the end of the study, CL18100F4-500 subjects showed significant increases in serum serotonin, gastrin, and interleukin-10 and decrease in interleukin-6 and cortisol levels. Participants' hematology, total blood chemistry, vital signs, and urinalysis parameters were within the normal ranges. No adverse events were reported. CONCLUSIONS: This short-duration, single-site clinical investigation demonstrates that CL18100F4 supplementation is tolerable, helps relieve constipation, reduces stress, and improves gastrointestinal function, sleep quality, and general wellness in adults. TRIAL REGISTRATION: Clinical Trials Registry- India (CTRI/2020/11/029320); Registered on 24/11/2020. Available at: http://ctri.nic.in/Clinicaltrials/showallp.php?mid1=49391&EncHid=&userName=CL18100F4.

A systematic review of traditional uses, phytochemistry, pharmacology and toxicity of Epimedium koreanum Nakai.

ETHNOPHARMACOLOGICAL RELEVANCE: Epimedium koreanum Nakai (E. koreanum), a member of the genus Epimedium in the family Berberidaceae, is a well-known and well-liked traditional herb used as a "kidney tonic". For thousands of years, it has been utilized for renal yang deficiency, impotence, spermatorrhea, impotence, weakness of tendons and bones, rheumatic paralysis and discomfort, numbness, and constriction. AIM OF THE STUDY: The paper aims to comprehensively in-depth, and methodically review the most recent research on the traditional uses, phytochemistry, pharmacology, and toxicity of E. koreanum. MATERIALS AND METHODS: Scientific databases including Web of Science, PubMed, Google Scholar, Elsevier, Springer, ScienceDirect, Baidu Scholar, and CNKI and medicine books in China were searched for relevant information on E. koreanum. RESULTS: In traditional uses, E. koreanum is frequently used to treat various diseases like erectile dysfunction, infertility, rheumatoid arthritis, osteoporosis, asthma, kidney-yang deficiency syndrome, etc. To date, more than 379 compounds have been discovered from various parts of E. koreanum, including flavonoids, lignans, organic acids, terpenoids, hydrocarbons, dihydrophenanthrene derivatives, alkaloids, and others. Research has revealed that the compounds and crude extracts have a wide range of pharmacological effects on the reproductive, cardiovascular, and nervous systems, as well as anti-osteoporosis, anti-tumor, antioxidant, anti-inflammatory, immunomodulatory, hepatoprotective, and antiviral properties. Besides, the crude extracts show potential hepatotoxicity. CONCLUSION: Based on recent domestic and international research investigations, E. koreanum contains a wealth of chemical components with pronounced pharmacological activities. Its traditional uses are numerous, and the majority of these traditional uses have been supported by contemporary pharmacological investigations. Crude extracts, on the other hand, can result in hepatotoxicity. Therefore, additional in vivo and in vitro experimental research on the pharmacology and toxicology of E. koreanum are required in the future to assess its safety and efficacy. This will give a firmer scientific foundation for its safe application and the development of new drugs in the future.

Comparative pharmacokinetics and tissue distribution of polydatin, resveratrol, and emodin after oral administration of Huzhang and Huzhang-Guizhi herb-pair extracts to rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Huzhang-Guizhi herb pair (HGHP), composed of Polygonum cuspidatum (Huzhang [HZ] in Chinese, the root of Polygonum cuspidatum Sieb. & Zucc.) and Ramulus Cinnamomi (Guizhi [GZ] in Chinese, the dried twig of Cinnamomum cassia Presl.), is a popular herb pair commonly used to treat arthritis and involved in many Chinese prescriptions. In order to reveal the influence of GZ on HZ on bioavailability, the pharmacokinetic behaviors and tissue distribution variations of the three analytes from HZ were detected between oral administration of HZ and HGHP extracts to rats. MATERIALS AND METHODS: Male Sprague-Dawley rats were randomly assigned to two groups for pharmacokinetics study and eight groups for tissues distribution research with the equivalent dose of 18 g crude HZ/kg. Assays for analytes from HZ (polydatin, resveratrol, emodin) were developed and validated using high performance liquid chromatography with ultraviolet detection (HPLC-UV). RESULTS: Part pharmacokinetic parameters including area under the concentration-time curve (AUC), the maximum plasma concentration (Cmax), biological half-life (t1/2), mean residence time (MRT), time to peak concentration (Tmax), clearance rate/bioavailability (CL/F) and volume of distribution/bioavailability (Vd/F) showed significant difference (P < 0.05) after oral administration of HGHP, as compared to those of HZ. The three analytes could be detected in heart, liver, spleen, lung, kidney and brain. Compared with the HZ group, AUC0-t of polydatin in heart, liver and kidney increased significantly (p < 0.05) while that in spleen decreased significantly (p < 0.05); AUC0-t of resveratrol in all detected tissues increased conspicuously (p < 0.05) in the HGHP group; AUC0-t of emodin in heart, liver, spleen, lung, and kidney increased conspicuously (p < 0.05), and decreased obviously (p < 0.05) in brain in the HGHP group. CONCLUSIONS: GZ could strongly influence the pharmacokinetic parameters and tissue distribution characteristics of polydatin, resveratrol and emodin in rats when administrated with HZ or HGHP extracts. It might provide a reference for further explanation of the compatibility mechanism and the clinical application of HGHP.

Monitoring the feeding and parental care behavior of a pair of free-living owls (Tyto furcata) in the nest during the reproductive period in Rio de Janeiro, Brazil / Monitoramento do comportamento alimentar e cuidado parental de um casal de corujas de vida livre (Tyto furcata) no ninho durante o período reprodutivo no Rio de Janeiro, Brasil

Abstract The American Barn Owl (Tyto furcata) lives in urban, periurban and wild environments and feeds mainly on small rodents, meaning it has great importance in the biological control of pests. The aim of this work was to describe the reproductive, parental and eating habits of a pair of American barn owls naturally living outside a residence in the urban area of the municipality of Campos dos Goytacazes, Rio de Janeiro state, Brazil. A wood box was installed on an outside wall of the home, monitored by a video camera. A spreadsheet was created to keep track of the observations recorded. The female laid four eggs, and after an incubation period of 30-32 days all the eggs hatched, but only two chicks survived after cannibalism among the chicks. Initially, the male provided the food to the chicks and the female remained in the nest caring for the brood. After approximately a month, the female also began to leave the nest and return with prey, which was offered to the chicks, with the male also continuing this behavior. The chicks left the nest in September, 2017. The data obtained show the existence of cooperation and division of tasks between male and female owls during the reproductive period.

Resumo A coruja-das-torres americana (Tyto furcata) vive em ambientes urbanos e se alimenta principalmente de pequenos roedores, sendo de grande importância no controle biológico de pragas. O objetivo deste trabalho foi descrever os hábitos alimentares, parentais e reprodutivos de um casal de corujas-das-torres americanas, naturalmente vivendo fora de uma residência na zona urbana do município de Campos dos Goytacazes, estado do Rio de Janeiro, Brasil. Uma caixa de madeira foi instalada em uma parede externa da casa, monitorada por uma câmera de vídeo. Uma planilha foi criada para manter o controle das observações registradas. A fêmea pôs quatro ovos, e após período de incubação de 30-32 dias todos os ovos eclodiram, mas apenas dois filhotes sobreviveram após o canibalismo entre os filhotes. Inicialmente, o macho fornecia a comida aos filhotes e a fêmea permanecia no ninho cuidando da ninhada. Depois de cerca de um mês, a fêmea também começou a sair do ninho e voltar com a presa, que era oferecida aos filhotes, com o macho também continuando com esse comportamento. Os filhotes deixaram o ninho em setembro de 2017. Os dados obtidos mostram a existência de cooperação e divisão de tarefas entre corujas machos e fêmeas durante o período reprodutivo.

Oral glutamine dipeptide or oral glutamine free amino acid reduces burned injury progression in rats / O dipeptídeo de glutamina oral ou aminoácido livre de glutamina oral reduz a progressão da lesão por queimadura em ratos

Abstract This study was carried out to evaluate the effect of Glutamine, as a dipeptide or a free amino acid form, on the progression of burn injuries in rats. Thirty male Wistar rats were burned with a comb metal plate heated in boiling water (98 °C) for three minutes, creating four rectangular full-thickness burn areas separated by three unburned interspaces (zone of stasis) in both dorsum sides. The animals were randomized into three groups (n=10): saline solution (G1-Control) and treated groups that orally received Glutamine as dipeptide (G2-Dip) or free amino acid (G3-FreeAA). Two and seven days after burn injury, lesions were photographed for unburned interspaces necrosis evolution assessment. Seven days after injury, glutathione seric was measured and histopathological analysis was performed. By photographs, there was a significant reduction in necrosis progression in G3-Free-AA between days two and seven. Histopathological analysis at day 7 showed a significantly higher stasis zone without necrosis and a higher number of fibroblasts in G2-Dip and G3-FreeAA compared with G1-Control. Also, glutathione serum dosage was higher in G2-Dip. The plasmatic glutathione levels were higher in the G2-Dip than the G1-Control, and there was a trend to higher levels in G3-FreeAA. The reduction in histological lesions, greater production of fibroblasts, and greater amounts of glutathione may have benefited the evolution of burn necrosis, which showed greater preservation of interspaces.

Resumo Este estudo foi realizado para avaliar o efeito da Glutamina, como um dipeptídeo ou forma de aminoácido livre, na progressão de queimaduras em ratos. Trinta ratos Wistar machos foram queimados com um pente de metal aquecido em água fervente (98 °C) por três minutos, criando quatro áreas retangulares queimadas separadas por três interesespaços não queimados (zona de estase) em ambos os lados do dorso. Os animais foram randomizados em três grupos (n = 10): solução salina (G1-Controle) e grupos tratados que receberam glutamina via oral como dipeptídeo (G2-Dip) ou aminoácido livre (G3-FreeAA). Dois e sete dias após a queimadura, as lesões foram fotografadas para avaliação da evolução da necrose entre os espaços não queimados. Sete dias após a lesão, foi dosada a glutationa sérica e realizada análise histopatológica. Pelas fotografias, houve uma redução significativa na progressão da necrose no G3-Free-AA entre os dias dois e sete. A análise histopatológica no dia 7 mostrou uma zona de estase significativamente maior sem necrose e número mais elevado de fibroblastos em G2-Dip e G3-FreeAA em comparação com G1-Controle. Os níveis plasmáticos de glutationa foram maiores no G2-Dip em relação ao G1-Controle, e houve tendência a níveis mais elevados no G3-FreeAA. A redução das lesões histológicas, maior produção de fibroblastos, maior quantidade de glutationa podem ter beneficiado a evolução da necrose da queimadura, que mostrou maior preservação dos interespaços.

Prediction of visceral leishmaniasis incidence using the Seasonal Autoregressive Integrated Moving Average model (SARIMA) in the state of Maranhão, Brazil / Previsão da incidência da leishmaniose visceral usando o modelo de média móvel integrado autorregressivo sazonal (SARIMA) no Maranhão, Brasil

Abstract Visceral leishmaniasis (VL) is an infectious disease predominant in countries located in the tropics. The prediction of occurrence of infectious diseases through epidemiologic modeling has revealed to be an important tool in the understanding of its occurrence dynamic. The objective of this study was to develop a forecasting model for the incidence of VL in Maranhão using the Seasonal Autoregressive Integrated Moving Average model (SARIMA). We collected monthly data regarding VL cases from the National Disease Notification System (SINAN) corresponding to the period between 2001 and 2018. The Box-Jenkins method was applied in order to adjust a SARIMA prediction model for VL general incidence and by sex (male or female) for the period between January 2019 and December 2013. For 216 months of this time series, 10,431 cases of VL were notified in Maranhão, with an average of 579 cases per year. With regard to age range, there was a higher incidence among the pediatric public (0 to 14 years of age). There was a predominance in male cases, 6437 (61.71%). The Box-Pierce test figures for overall, male and female genders supported by the results of the Ljung-Box test suggest that the autocorrelations of residual values act as white noise. Regarding monthly occurrences in general and by gender, the SARIMA models (2,0,0) (2,0,0), (0,1,1) (0,1,1) and (0,1,1) (2, 0, 0) were the ones that mostly adjusted to the data respectively. The model SARIMA has proven to be an adequate tool for predicting and analyzing the trends in VL incidence in Maranhão. The time variation determination and its prediction are decisive in providing guidance in health measure intervention.

Resumo A leishmaniose visceral (LV) é uma doença de natureza infecciosa, predominante em países de zonas tropicais. A predição de ocorrência de doenças infecciosas através da modelagem epidemiológica tem se revelado uma importante ferramenta no entendimento de sua dinâmica de ocorrência. O objetivo deste estudo foi desenvolver um modelo de previsão da incidência da LV no Maranhão usando o modelo de Média Móvel Integrada Autocorrelacionada Sazonal (SARIMA). Foram coletados os dados mensais de casos de LV através do Sistema de Informação de Agravos de Notificação (SINAN) correspondentes ao período de 2001 a 2018. O método de Box-Jenkins foi aplicado para ajustar um modelo de predição SARIMA para incidência geral e por sexo (masculino e feminino) de LV para o período de janeiro de 2019 a dezembro de 2023. Durante o período de 216 meses dessa série temporal, foram registrados 10.431 casos de LV no Maranhão, com uma média de 579 casos por ano. Em relação à faixa etária, houve maior registro no público pediátrico (0 a 14 anos). Houve predominância do sexo masculino, com 6437 casos (61,71%). Os valores do teste de Box-Pierce para incidência geral, sexo masculino e feminino reforçados pelos resultados do teste Ljung-Box sugerem que as autocorrelações de resíduos apresentam um comportamento de ruído branco. Para incidência mensal geral e por sexo masculino e feminino, os modelos SARIMA (2,0,0) (2,0,0), (0,1,1) (0,1,1) e (0,1,1) (2, 0, 0) foram os que mais se ajustaram aos dados, respectivamente. O modelo SARIMA se mostrou uma ferramenta adequada de previsão e análise da tendência de incidência da LV no Maranhão. A determinação da variação temporal e sua predição são determinantes no norteamento de medidas de intervenção em saúde.

Effect of Agaricus blazei Murill on exploratory behavior of mice-model / Efeito de Agaricus blazei Murill no comportamento exploratório de modelo de camundongo

Abstract Increased anxiety and depressive symptoms have reported to be its association with long term illness. Because of having unwanted effects of newly available drugs, patients administering anxiolytic drugs usually discontinue the treatment before they are completely recovered. Therefore, there is a serious need to develop new anxiolytic drugs. The anxiolytic effect of hydro-alcoholic extract of Agaricus blazei in animal models was assessed. 24 male mice (Mus musculus genus) were included in the study. Four groups were prepared and each group contained six animals. The groups were vehicle control, positive control (diazepam 1.0 mg/kg, i.p.) as well as two treatment groups receiving Agaricus blazei hydro-alcoholic extract at a dose of 136.50 mg/kg and 273.0 mg/kg orally. The Marble burying test, Nestlet shredding test and Light and Dark box test used to assess anxiolytic activity. Mice administered with diazepam 1.0 mg/kg, i.p. while hydro-alcoholic extract of AbM (136.50 and 273.0 mg/kg, respectively) was administered via oral route which exhibited marked reduction in number of marbles-burying as compared to vehicle control group. Mice administered with diazepam 1.0 mg/kg, i.p. and Oral administration of hydro-alcoholic extract of AbM (136.50 and 273.0 mg/kg, respectively) exhibited significant decrease in nestlet shredding in comparison to vehicle control group. The oral administration of hydro-alcoholic extract at a dose of 136.5mg/kg and 273mg/kg showed elevation in time spent in light box and was comparable to standard treated group while time spent by mice following oral administration of hydro-alcoholic extract of Agaricus blazei at a dose of 273.0 mg/kg also showed elevation and was found to be more near to standard treated group (diazepam 1 mg/kg, i.p.).

Resumo O aumento da ansiedade e dos sintomas depressivos têm relatado sua associação com doenças de longa duração. Por causa dos efeitos indesejáveis dos novos medicamentos disponíveis, os pacientes que administram medicamentos ansiolíticos geralmente interrompem o tratamento antes de estarem completamente recuperados. Portanto, há uma necessidade séria de desenvolver novos medicamentos ansiolíticos. Foi avaliado o efeito ansiolítico do extrato hidroalcoólico de Agaricus blazei em modelos animais. Vinte e quatro camundongos machos (gênero Mus musculus) foram incluídos no estudo. Quatro grupos foram preparados, e cada grupo continha seis animais. Os grupos foram controle de veículo, controle positivo (diazepam 1,0 mg/kg, i.p.), bem como dois grupos de tratamento recebendo extrato hidroalcoólico de Agaricus blazei na dose de 136,50 mg/kg e 273,0 mg/kg por via oral. O teste de enterrar Marble, o teste de retalhamento Nestlet e o teste de caixa clara e escura são usados ​​para avaliar a atividade ansiolítica. Camundongos foram administrados com diazepam 1,0 mg/kg, i.p., enquanto o extrato hidroalcoólico de AbM (136,50 e 273,0 mg/kg, respectivamente) foi administrado por via oral, que exibiu redução acentuada no número de mármores enterrados em comparação com o grupo de controle de veículo. Camundongos administrados com diazepam 1,0 mg/kg, i.p. e a administração oral de extrato hidroalcoólico de AbM (136,50 e 273,0 mg/kg, respectivamente) exibiu diminuição significativa na trituração de ninhos em comparação ao grupo de controle de veículo. A administração oral de extrato hidroalcoólico na dose de 136,5mg/kg e 273mg/kg mostrou elevação no tempo gasto na caixa de luz e foi comparável ao grupo tratado padrão, enquanto o tempo gasto por camundongos após a administração oral de extrato hidroalcoólico de Agaricus blazei na dose de 273,0 mg/kg também mostrou elevação e foi mais próximo do grupo tratado padrão (diazepam 1 mg/kg, ip).

Exploration of the mechanisms of improving learning and memory in the offspring of aging pregnant mice by supplementation with Paris polyphylla polysaccharide based on the P19-P53-P21 and Wnt/ß-catenin signaling pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: First recorded in "Sheng Nong's herbal classic", Paris polyphylla is used to treat diseases, such as convulsions, head shaking and tongue fiddling, and epilepsy. Studies have shown that the ability of three Liliaceae polysaccharides in improving learning and memory may be related to the P19-P53-P21 and Wnt/ß-catenin signaling pathways. Moreover, a link between these two signaling pathways and the possible neuroprotective impact of Paris polyphylla polysaccharide has been proposed. AIM OF THE STUDY: We explored the mechanisms of improving learning and memory in the offspring of pre-pregnant parental mice and D-galactose-induced aging pregnant mice by supplementation with P. polyphylla polysaccharide based on the P19-P53-P21 and Wnt/ß-catenin signaling pathways. STUDY DESIGN AND METHODS: After 3 weeks of supplementation of D-galactose-induced pre-pregnant parental mice with P. polyphylla polysaccharide component 1 (PPPm-1), the male and female parental mice mated in cages. The D-galactose-induced pregnant mice were continued to be supplemented with PPPm-1 for 18 days before delivery of the offspring. Behavioral experiments (Morris water maze and dark avoidance experiments) were conducted on the offspring mice born 48 days later to determine whether PPPm-1 had the effect of improving their learning and memory. Based on the P19/P53/P21 and Wnt/ß-catenin signaling pathways, the mechanisms of PPPm-1 in improving learning and memory in offspring mice were further investigated. RESULTS: Offspring mice administered low- or high-dose PPPm-1 exhibited stronger motor and memory abilities in behavioral experiments than the aging model of offspring mice. Enzyme-linked immunosorbent assay and real-time polymerase chain reaction revealed that the expressions of P19 and P21 mRNA and protein were inhibited in offspring mice administered low- and high-dose PPPm-1. However, P53 expression was inhibited in the low-dose PPPm-1 offspring group but promoted in the high-dose PPPm-1 offspring group. Additionally, PPPm-1 could effectively activate the Wnt/ß-catenin signaling pathway, promote the expressions of Wnt/1, ß-catenin, CyclinD1, and TCF-4 mRNA and protein, and inhibit GSK-3ß mRNA and protein expression to improve the learning and memory abilities of offspring mice. CONCLUSION: Thus, PPPm-1 improved the learning and memory abilities in the offspring of aging pregnant mice by acting on the P19-P53-P21 and Wnt/ß-catenin signaling pathways.

Wuzi Yanzong administration alleviates Sertoli cell injury by recovering AKT/mTOR-mediated autophagy and the mTORC1-mTROC2 balance in aging-induced testicular dysfunction.

ETHNOPHARMACOLOGICAL RELEVANCE: Wuzi Yanzong Prescription (WZ), a classic traditional Chinese medicine formula, has the properties of kidney nourishing and essence strengthening, and it is widely used to treat male infertility with a long history. Sertoli cells are injured with aging, resulting in testicular dysfunction, and WZ effectively rejuvenates the age-related decline of testicular function. However, whether the therapeutic effects of WZ on aging-related testicular dysfunction are dependent on the restoration of Sertoli cell function remains unclear. AIM OF THE STUDY: In a mouse model of natural aging, we explored the protective effects of WZ and its potential mechanisms. MATERIALS AND METHODS: Fifteen-month-old C57BL/6 mice were randomized to receive either standard diet or WZ (2 and 8 g/kg) for 3 months. Meanwhile, 10 1-month-old mice were considered the adult control group and received standard diet for 3 months. The testis and epididymis were rapidly collected, and the sperm quality, testicular histology, Sertoli cell numbers, tight junction (TJ) ultrastructure, and blood-testis barrier-associated protein expression and localization were assessed. RESULTS: WZ significantly increased sperm concentration and sperm viability, improved the degenerative histomorphology and elevated the seminiferous epithelium height. Furthermore, WZ increased the number of Sertoli cells, restored the ultrastructure of the Sertoli cell TJ, and upregulated the expression of TJ-associated proteins (zonula occludens-1 and Claudin11), ectoplasm specialized-associated proteins (N-Cadherin, E-Cadherin and ß-Catenin), and gap junction-associated protein (connexin 43), but did not affect the expression of Occludin and cytoskeletal protein (Vimentin). In addition, WZ did not change the localization of zonula occludens-1 and ß-Catenin in aged testis. Moreover, WZ increased the expression of autophagy-associated proteins (light chain 3 beta and autophagy related 5) and decreased the expression of p62, phosphorylated mammalian target of rapamycin, and phosphorylated AKT in Sertoli cells. Finally, we found that WZ attenuated mTOR complex 1 (mTORC1) activity and upregulated mTORC2 activity, as evidenced by inhibition of the expression of the regulatory-associated protein of mTOR, phosphorylated p70 S6K, and phosphorylated ribosomal protein s6 and enhancement of the expression of Rictor in the Sertoli cells of aging mice. CONCLUSIONS: WZ improves the injury of Sertoli cells by restoring AKT/mTOR-mediated autophagy and the mTORC1-mTROC2 balance in Sertoli cells during aging. Our findings provide a new mechanism of WZ in the treatment of aging-induced testicular dysfunction.

Promising anti-ovarian aging herbal formulation He's Yangchao promotes in vitro maturation of oocytes from advanced maternal age mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Marveled at the discovery of artemisinin, the world's expectations for traditional Chinese medicine are rising. He's Yangchao formula (HSYC) is a traditional Chinese herbal formula with the effects of tonifying kidney and essence, and reconciling yin and yang. It has been clinically proven to have anti-ovarian aging effects. Age is the primary cause of diminished ovarian reserve and assisted reproductive failure in women, whether HSYC has the potential to improve in vitro maturation of oocytes from advanced maternal age (AMA) mice has yet to be determined. AIM OF THE STUDY: This study aims to evaluate the efficacy and possible mechanism of HSYC in promoting in vitro maturation of oocytes from AMA mice. MATERIALS AND METHODS: The GV oocytes were obtained from young and aged mice. The GV oocytes from young mice were cultured in drops of M16 medium, and the GV oocytes from AMA mice were randomly divided four groups: Vehicle group (cultured in 90% M16 medium +10% blank serum), Low HSYC group (cultured in 90% M16 medium + 10% Low HSYC-medicated serum), High-HSYC group (cultured in 90% M16 medium +10% High HSYC-medicated serum), and Quercetin group (cultured in M16 medium supplemented with 10 µM quercetin). The rates of first polar body extrusion, reactive oxygen species (ROS), intracellular calcium, and mitochondrial membrane potential levels in each groups were observed. In addition, expression levels of mitochondrial function, autophagy, DNA damage, and antioxidant-related proteins were assessed. RESULTS: Supplementation of HSYC in vitro alleviated age-associated meiotic progression defects in maternally aged oocytes. Importantly, HSYC supplementation eliminated the age-related ROS accumulation to suppress DNA damage and autophagy during the in vitro maturation of maternally aged oocytes. Meanwhile, the mitochondrial function was improved after HSYC treatment, as manifested by higher mitochondrial membrane potential and lower Ca2+ levels. Furthermore, we found that HSYC supplementation during in vitro maturation of maternally aged oocytes upregulated the expression level of SIRT3, a crucial protein in regulating mitochondrial function. Consistently, the expression levels of the SOD2, PCG1α, and TFAM were increased, while the SOD2 acetylation level was decreased, which further proved its antioxidant function. CONCLUSIONS: HSYC supplementation promotes in vitro maturation of oocytes from AMA mice mainly via improving mitochondrial function and alleviating oxidative stress. The mechanism may be related to the regulation of SIRT3-dependent deacetylation of the SOD2 pathway.

The traditional use of native Brazilian plants for male sexual dysfunction: Evidence from ethnomedicinal applications, animal models, and possible mechanisms of action.

ETHNOPHARMACOLOGICAL RELEVANCE: Sexual dysfunction is a multifactorial health condition characterized by distressing disturbances in the sexual response and libido, leading to an inability to maintain penile erection and achieve pleasure. Considering the huge Brazilian biodiversity, many plants are traditionally used for aphrodisiac purposes. However, the use of native medicinal plants as sexual boosters in Brazil has been poorly studied. AIM OF THE STUDY: This review focuses on the composition, pharmacology, and results of experimental trials of the main native plants used in Brazilian folk medicine with alleged aphrodisiac effects. We aimed to provide a state-of-the-art reference for research on herbs for the treatment of male sexual dysfunction by summarizing and discussing the main studies found. MATERIALS AND METHODS: The relevant information was collected by searching keywords (aphrodisiac, sexual tonic, sexual stimulant, sexual vigor stimulant, sexual impotency, erectile dysfunction, etc.) from books containing primary surveys conducted in the original communities and bibliographic surveys prepared by authors linked to the national academic and scientific environment edited in Brazil. Preclinical and clinical studies of the compiled plant species were performed using scientific databases (Scopus, PubMed, SciELO, and SciFinder). RESULTS: Seventy-four plant species belonging to 44 families used in Brazil to treat sexual dysfunction were compiled from ethnopharmacological literature. Fourteen plants, including Pfaffia glomerata (Spreng.) Pedersen, Aspidosperma quebracho-blanco Schltdl., Anemopaegma arvense (Vell.) Stellfeld ex de Souza, Mimosa pudica L., Heteropterys tomentosa A. Juss., Trichilia catigua A. Juss., and Turnera diffusa Willd. ex Schult. were pharmacologically studied to confirm these therapeutic properties. Probable modes of action include antioxidant and androgenic activities, inhibition of the PDE5 enzyme, increase in NO levels, and activation of dopaminergic and noradrenergic pathways. In addition, several different species popularly known as "catuaba" were identified, leading to adulterations and controversial effects. CONCLUSION: The overall results of the present review of Brazilian folk literature reveal that Brazil has a long tradition of using plants with potential aphrodisiac effects. However, further research is required to identify, characterize, and standardize the active ingredients and herbal preparations used in aphrodisiacs.

Yiqi Jiedu decoction attenuates radiation injury of spermatogenic cells via suppressing IκBα/NF-κB pathway-induced excessive autophagy and apoptosis.

ETHNOPHARMACOLOGICAL RELEVANCE: The prescription of Yiqi Jiedu decoction (YQJD) originated from the classic Chinese herbal prescriptions of Danggui Buxue Decoction and Wuzi Yanzong Pill. A previous study has shown that 4 Gy irradiation induced the apoptosis of spermatocytes and revealed autophagosomes in cells exposed to radiation. YQJD decoction has the effect of preventing radiation injury. AIM OF THE STUDY: We used spermatocytes (GC-2spd cell line) to investigate the relationship between autophagy and apoptosis of spermatogenic cells after radiation, and the mechanisms of YQJD decoction. MATERIALS AND METHODS: Establish an in vitro radiation injury model by irradiating GC-2spd cells with 60Co γ-rays (4 Gy or 8 Gy). Autophagy agonists, autophagy inhibitors and YQJD were used to intervene cells. Cell apoptosis and inflammatory factors were measured. NF-κB localization was observed by immunofluorescence. Autophagy and apoptosis-related proteins and IκBα/NF-κB pathway factors were detected. RESULTS: Ionizing radiation promoted the growth of spermatogenic autophagosomes. After radiation, NF-κB was translocated to the nucleus, inflammatory factors were secreted, and IκBα/NF-κB pathway was activated, which promoted autophagy and apoptosis. YQJD decoction can inhibit the phosphorylation of IκBα/NF-κB pathway related factors, regulate the expression of Beclin-1 and Bcl-2 proteins, and inhibit the occurrence of autophagy and apoptosis of irradiated spermatocyte. CONCLUSIONS: The research results indicate that ionizing radiation can activate the IκBα/NF-κB signaling pathway in spermatocytes, promote cell autophagy and apoptosis by regulating the expression of Beclin-1 and Bcl-2 factors. The YQJD decoction inhibits the IκBα/NF-κB signaling pathway so as to regulate Beclin-1 and Bcl-2.