The fate of flavonoids after oral administration: a comprehensive overview of its bioavailability.

Despite advancements in synthetic chemistry, nature remains the primary source of drug discovery, and this never-ending task of finding novel and active drug molecules will continue. Flavonoids have been shown to possess highly significant therapeutic activities such as anti-inflammatory, anti-oxidant, anti-viral, anti-diabetic, anti-cancer, anti-aging, neuroprotective, and cardioprotective, etc., However, it has been found that orally administered flavonoids have a critical absorption disorder and, therefore, have low bioavailability and show fluctuating pharmacokinetic and pharmacodynamic responses. A detailed investigation is required to assess and analyze the variation in the bioavailability of flavonoids due to interactions with the intestinal barrier. This review will emphasize on the bioavailability and the pharmacological applications of flavonoids, key factors affecting their bioavailability, and strategies for enhancing bioavailability, which may lead to deeper understanding of the extent of flavonoids as a treatment and/or prevention for different diseases in clinics.

Radiofrequency thermocoagulation of the sulcus bottom in type II focal cortical dysplasia-related epilepsy with tapered implantation of electrodes: a case report.

We report a 15-year-old male patient with recurrent epileptic seizures for 12 years. Oral multiple drugs do not work well to his condition. MRI FLAIR scans revealed focal cortical dysplasia type II in the right parietal lobe. The diagnosis of the patient was drug-refractory epilepsy, FCD-related secondary epilepsy. According to the shape of the FCD lesion, electrodes were implanted in a tapered pattern along the bottom of the sulcus to completely destroy the focus. Magnetic resonance imaging at 6 months after surgery revealed that the FCD at the sulcus bottom was completely destroyed. After 26 months of follow-up, the patient had undergone no epileptic seizures, reaching Engel class I. For FCD that are located deep in the brain and adjacent to functional areas, craniotomy has a high risk. And stereoelectroencephalography-guided radiofrequency thermocoagulation may be a preferred treatment.

Exploring the multicomponent synergy mechanism of Zuogui Wan on postmenopausal osteoporosis by a systems pharmacology strategy.

OBJECTIVE: To explore the multi-component synergistic mechanism of Zuogui Wan (, ZGW) in treating postmenopausal osteoporosis (PMOP). METHODS: The main components and target genes of ZGW were screened via the Traditional Chinese Medicine Systems Pharmacology (TCMSP). In addition, the target gene sets of PMOP were derived from the GeneCards and Online Mendelian Inheritance in Man databases. The search tool for recurring instances of neighbouring genes (STRING) 11.0 software was used to analyze the interaction among intersecting genes. Cytoscape 3.6.1 software and the Matthews correlation coefficient (MCC) algorithm were used to screen the core genes. Fifty Sprague-Dawley female rats were randomly divided into the sham-operated (Sham) group and the four ovariectomized (OVX) subgroups. Rats subjected to Sham or OVX were administered with the vehicle (OVX, 1 mL water/100 g weight), 17ß-estradiol (E2, 50 µg·kg-1·d-1), and lyophilized powder of ZGW at a low dose of 2.3 (ZGW-L) and high dose of 4.6 (ZGW-H) g·kg-1·d-1 for three months. The bone density and bone strength were assessed using dual-energy X-ray and three-point bending tests, respectively. Furthermore, enzyme-linked immun-osorbent assay, Hematoxylin-eosin staining, and western blot analysis were used to determine the potential pharmacological mechanisms of action of ZGW in PMOP. RESULTS: A total of 117 active compounds of ZGW were screened from the TCMSP. Furthermore, 108 intersecting genes of drugs and diseases were identified. Using STRING software and the MCC algorithm, ten core genes, including C-X-C chemokine living 8 (CXCL8), C-C chemokine receptor type 2 (CCR2), alpha-2a active receptor (ADRA2A), melatonin receptor type 1B (MTNR1B), and amyloid-beta A4 protein (APP), were identified. The anti-osteoporosis regulation network of ZGW was constructed using the Cytoscape software. The animal experiments demonstrated that ZGW groups significantly reduced the serum levels of ß-C-terminal telopeptide of type I collagen (ß-CTX) and increased serum levels of bone-specific alkaline phosphatase (BALP) (P < 0.05, P < 0.01). The OVX group exhibited a significant decrease in bone mineral density and bone strength compared with the Sham group (P < 0.01). Moreover, treatment with ZGW resulted in increased trabecular thickness, improved arrangement of trabecular structure, and reduced empty bone lacunae. Furthermore, treatment with ZGW significantly increased the protein expression of CXCL8, ADRA2A, and CCR2 (P < 0.05, P < 0.01), and significantly decreased the protein expression of Runx2 (P < 0.01). Furthermore, the ZGW and E2 groups demonstrated significantly increased BMD (P < 0.05, P < 0.01), improved bone strength (P < 0.05, P < 0.01), reduced expression of CXCL8, ADRA2A, and CCR2, and increased runt-related transcription factor 2 levels in bone tissue (P < 0.05, P < 0.01) compared with the OVX group. However, there were no significant differences in MTNR1B and APP expression among the groups. CONCLUSION: ZGW shows synergistic mechanisms in PMOP through multiple components, targets, and pathways.

Exploration of ethnomedicinal plants and their practices in human and livestock healthcare in Haripur District, Khyber Pakhtunkhwa, Pakistan.

BACKGROUND: The utilization of plants and plant resources for various ethnobotanical purposes is a common practice in local towns and villages of developing countries, especially in regard to human and veterinary healthcare. For this reason, it is important to unveil and document ethnomedicinal plants and their traditional/folk usage for human and livestock healthcare from unexplored areas. Here we advance our findings on ethnomedicinal plants from Haripur District, Pakistan, not only for conservation purposes, but also for further pharmacological screenings and applied research. METHODOLOGY: Information of ethnomedicinal plants was obtained using a carefully planned questionnaire and interviews from 80 local people and traditional healers (Hakims) in Haripur District, Pakistan, from 2015 to 2017. Informed consent was obtained from each participant before conducting the interview process. Quantitative ethnobotanical indices, such as relative frequency of citation (RFC), use value (UV) and Jaccard index (JI), were calculated for each recorded species. Correlation analysis between the RFC and UV was tested by Pearson's correlation, SPSS (ver. 16). RESULTS: A total of 80 plant species (33 herbs, 24 trees, 21 shrubs and 2 climbers) belonging to 50 families were being used in the study area to treat livestock and human diseases. Lamiaceae was the most dominant family with 7 species (8.7%), followed by Fabaceae with 6 species (7.5%), and Moraceae with 5 species (6.2%). Local people used different methods of preparation for different plant parts; among them, decoction/tea (22 species) was the popular method, followed by powder/grained (20 species) and paste/poultice (14 species). It was observed that most of the species (~ 12 to 16 species) were utilized to treat human and livestock digestive system-related problems, respectively. The Jaccard index found that plant usage in two studies (District Abbottabad and Sulaiman Range) was more comparable. Local people mainly relied on folk medicines due to their rich accessibility, low cost and higher efficacy against diseases. Unfortunately, this important traditional knowledge is vanishing fast, and many medicinal plants are under severe threat. The most threats associated to species observed in the study area include Dehri, Garmthun, Baghpur, Najafpur and Pharala. CONCLUSION: The study has indicated that local people have higher confidence in the usage of ethnomedicinal plants and are still using them for the treatment of various ailments. Comparative analysis with other studies may strongly reflected the novel use of these plants, which may be due to the deep-rooted and unique socio-cultural setup of the study area. However, awareness campaigns, conservation efforts and pharmacological and applied research are required for further exploration and may be a step in the right direction to unveil prospective pharmaceuticals.