Diuretic effects of Hecogenin and Hecogenin acetate via aldosterone synthase inhibition.

Hecogenin (HEC) is a steroidal saponin found in many plant species and serves as a precursor for steroidal drugs. The diuretic effects of HEC and its derivative, hecogenin acetate (HA), remain largely unexplored. The present study aimed to explore the potential diuretic effects of HEC and HA compared to furosemide (FUR) and spironolactone (SPIR). Additionally, the study aimed to explore the underlying mechanism particularly focusing on aldosterone synthase gene expression. Fifty-four Sprague-Dawley rats were allocated into nine groups (Group 1-9). Group 1 (control) received the vehicle, Groups 2 received FUR 10 mg/kg, Group 3, 4, and 5 were given HEC, while Groups 6, 7 and 8 received HA i.p at doses of 5, 10, and 25 mg/kg, respectively. Group 9 received SPIR i.p at the dose of 25 mg/kg. Urine volume, diuretic index and diuretic activity were monitored at 1, 2, 3, 4, 5, 6, and 24 h post-administration. Treatment was given daily for seven days. After that, rats were sacrificed and blood was collected for serum electrolytes determination. Adrenal glands were dissected out for gene expression studies. The results revealed that HEC and HA at the administered doses significantly and dose-dependently increased urine and electrolyte excretion. These results were primarily observed at 25 mg/kg of each compound. Gene expression studies demonstrated a dose-dependent reduction in aldosterone synthase gene expression, suggesting aldosterone synthesis inhibition as a potential mechanism for their diuretic activity. Notably, HA exhibited more pronounced diuretic effects surpassing those of HEC. This enhanced diuretic activity of HA can be attributed to its stronger impact on aldosterone synthase inhibition. These findings offer valuable insights into the diuretic effects of both HEC and HA along with their underlying molecular mechanisms.

Lycopene attenuates chlorpyrifos-induced hepatotoxicity in rats via activation of Nrf2/HO-1 axis.

Chlorpyrifos (CPF), is an organophosphate pesticide that is widely used for agricultural purposes. However, it has well-documented hepatotoxicity. Lycopene (LCP) is a plant-derived carotenoid with antioxidant and anti-inflammatory activities. The present work was designed to evaluate the potential hepatoprotective actions of LCP against CPF-induced hepatotoxicity in rats. Animals were assigned into five groups namely: Group I (Control), Group II (LCP), Group III (CPF), Group IV (CPF + LCP 5 mg/kg), and Group V (CPF + LCP 10 mg/kg). LCP offered protection as evidenced by inhibiting the rise in serum activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) induced by CPF. This was confirmed histologically as LCP-treated animals showed liver tissues with less proliferation of bile ducts and periductal fibrosis. LCP significantly prevented the rise in hepatic content of malondialdehyde (MDA), depletion of reduced glutathione (GSH), and exhaustion of glutathione-s-transferase (GST) and superoxide dismutase (SOD). Further, LCP significantly prevented hepatocyte death as it ameliorated the increase in Bax and the decrease in Bcl-2 expression induced by CPF in liver tissues as determined immunohistochemically. The observed protective effects of LCP were further confirmed by a significant enhancement in heme oxygenase-1 (HO-1) and NF-E2-related factor 2 (Nrf2) expression. In conclusion, LCP possesses protective effects against CPF-induced hepatotoxicity. These include antioxidation and activation of the Nrf2/HO-1 axis.

Cordycepin- melittin nanoconjugate intensifies wound healing efficacy in diabetic rats.

The current study was designed to develop a nanoconjugate of cordycepin-melittin (COR-MEL) and assess its healing property in wounded diabetic rats. The prepared nanoconjugate has a particle size of 253.5 ± 17.4 nm with a polydispersity index (PDI) of 0.35 ± 0.04 and zeta potential of 17.2 ± 0.3 mV. To establish the wound healing property of the COR-MEL nanoconjugate, animal studies were pursued, where the animals with diabetes were exposed to excision and treated with COR hydrogel, MEL hydrogel, or COR-MEL nanoconjugate topically. The study demonstrated an accelerated wound contraction in COR-MEL nanoconjugate -treated diabetic rats, which was further validated by histological analysis. The nanoconjugate further exhibited antioxidant activities by inhibiting the accumulation of malondialdehyde (MDA) and exhaustion of superoxide dismutase (SOD) and glutathione peroxidase (GPx) enzymatic activities. The nanoconjugate further demonstrated an enhanced anti-inflammatory activity by retarding the expression of interleukin (IL)-6 and tumor necrosis factor (TNF)-α. Additionally, the nanoconjugate exhibits a strong expression of transforming growth factor (TGF)-ß1, vascular endothelial growth factor (VEGF)-A, and platelet-derived growth factor (PDGFR)-ß, indicating enrichment of proliferation. Likewise, nanoconjugate increased the concentration of hydroxyproline as well as the mRNA expression of collagen, type I, alpha 1 (Col 1A1). Thus, it is concluded that the nanoconjugate possesses a potent wound-healing activity in diabetic rats via antioxidant, anti-inflammatory, and pro-angiogenetic mechanisms.

Using genomic prediction to detect microevolutionary change of a quantitative trait.

Detecting microevolutionary responses to natural selection by observing temporal changes in individual breeding values is challenging. The collection of suitable datasets can take many years and disentangling the contributions of the environment and genetics to phenotypic change is not trivial. Furthermore, pedigree-based methods of obtaining individual breeding values have known biases. Here, we apply a genomic prediction approach to estimate breeding values of adult weight in a 35-year dataset of Soay sheep (Ovis aries). Comparisons are made with a traditional pedigree-based approach. During the study period, adult body weight decreased, but the underlying genetic component of body weight increased, at a rate that is unlikely to be attributable to genetic drift. Thus cryptic microevolution of greater adult body weight has probably occurred. Genomic and pedigree-based approaches gave largely consistent results. Thus, using genomic prediction to study microevolution in wild populations can remove the requirement for pedigree data, potentially opening up new study systems for similar research.

Melittin and diclofenac synergistically promote wound healing in a pathway involving TGF-ß1.

A dysregulation of the wound healing process can lead to the development of various intractable ulcers or excessive scar formation. Therefore it is essential to identify novel pharmacological strategies to promote wound healing and restore the mechanical integrity of injured tissue. The goal of the present study was to formulate a nano-complex containing melittin (MEL) and diclofenac (DCL) with the aim to evaluate their synergism and preclinical efficacy in an in vivo model of acute wound. After its preparation and characterization, the therapeutic potential of the combined nano-complexes was evaluated. MEL-DCL nano-complexes exhibited better regenerated epithelium, keratinization, epidermal proliferation, and granulation tissue formation, which in turn showed better wound healing activity compared to MEL, DCL, or positive control. The nano-complexes also showed significantly enhanced antioxidant activity. Treatment of wounded skin with MEL-DCL nano-complexes showed significant reduction of interleukin-6 (IL-6), IL-1ß, and tumor necrosis factor-α (TNF-α) pro-inflammatory markers that was paralleled by a substantial increase in mRNA expression levels of collagen, type I, alpha 1 (Col1A1) and collagen, type IV, alpha 1 (Col4A1), and hydroxyproline content as compared to individual drugs. Additionally, MEL-DCL nano-complexes were able to significantly increase hypoxia-inducible factor 1-alpha (HIF-1α) and transforming growth factor beta 1 (TGF-ß1) proteins expression compared to single drugs or negative control group. SB431542, a selective inhibitor of type-1 TGF-ß receptor, significantly prevented in our in vitro assay the wound healing process induced by the MEL-DCL nano-complexes, suggesting a key role of TGF-ß1 in the wound closure. In conclusion, the nano-complex of MEL-DCL represents a novel pharmacological tool that can be topically applied to improve wound healing.

Lipid-Based Nanoparticles as a Pivotal Delivery Approach in Triple Negative Breast Cancer (TNBC) Therapy.

Triple-negative breast cancer is considered the most aggressive type of breast cancer among women and the lack of expressed receptors has made treatment options substantially limited. Recently, various types of nanoparticles have emerged as a therapeutic option against TNBC, to elevate the therapeutic efficacy of the existing chemotherapeutics. Among the various nanoparticles, lipid-based nanoparticles (LNPs) viz. liposomes, nanoemulsions, solid lipid nanoparticles, nanostructured lipid nanocarriers, and lipid-polymer hybrid nanoparticles are developed for cancer treatment which is well confirmed and documented. LNPs include various therapeutic advantages as compared to conventional therapy and other nanoparticles, including increased loading capacity, enhanced temporal and thermal stability, decreased therapeutic dose and associated toxicity, and limited drug resistance. In addition to these, LNPs overcome physiological barriers which provide increased accumulation of therapeutics at the target site. Extensive efforts by the scientific community could make some of the liposomal formulations the clinical reality; however, the relatively high cost, problems in scaling up the formulations, and delivery in a more targetable fashion are some of the major issues that need to be addressed. In the present review, we have compiled the state of the art about different types of LNPs with the latest advances reported for the treatment of TNBC in recent years, along with their clinical status and toxicity in detail.

Cucurbitacin E glucoside from Citrullus colocynthis inhibits testosterone-induced benign prostatic hyperplasia in mice.

Benign prostatic hyperplasia (BPH) is a common disorder in men aged over 60 years and significantly contributes to the distressing lower urinary tract symptoms. Cucurbitacins are triterpene derivatives with diverse medicinal uses including prostate diseases. Cucurbitacin E glucoside was evaluated against testosterone-induced prostatic hyperplasia in mice. Our data indicate that it significantly inhibited the increase in prostate weight and prostate index. The compound ameliorated histopathological changes in prostatic architecture and inhibited the increase in glandular epithelial length induced by testosterone. These results were confirmed by decreased expression of cyclin D1 in prostatic tissues compared to those obtained from the testosterone-alone group. Also, it showed significant antioxidant activity as evidenced by inhibiting lipid peroxides accumulation, glutathione depletion and superoxide exhaustion. Further, it exhibited anti-inflammatory activity as it decreased cyclooxygenase-2 and interleukin-1ß protein expression in prostatic tissues. Masson's trichrome staining of prostate sections indicated obvious antifibrotic activity that was supported by decreased α-smooth muscle actin expression. In conclusion, Cucurbitacin E glucoside inhibits testosterone-induced experimental BPH in mice due to, at least partly, its antiproliferative, antioxidant, anti-inflammatory, and antifibrotic effects.

Chitosan Coated Microparticles Enhance Simvastatin Colon Targeting and Pro-Apoptotic Activity.

This work aimed at improving the targeting and cytotoxicity of simvastatin (SMV) against colon cancer cells. SMV was encapsulated in chitosan polymers, followed by eudragit S100 microparticles. The release of SMV double coated microparticles was dependent on time and pH. At pH 7.4 maximum release was observed for 6 h. The efficiency of the double coat to target colonic tissues was confirmed using real-time X-ray radiography of iohexol dye. Entrapment efficiency and particle size were used in the characterization of the formula. Cytotoxicity of SMV microparticles against HCT-116 colon cancer cells was significantly improved as compared to raw SMV. Cell cycle analysis by flow cytomeric technique indicated enhanced accumulation of colon cancer cells in the G2/M phase. Additionally, a significantly higher cell fraction was observed in the pre-G phase, which highlighted enhancement of the proapoptotic activity of SMV prepared in the double coat formula. Assessment of annexin V staining was used for confirmation. Cell fraction in early, late and total cell death were significantly elevated. This was accompanied by a significant elevation of cellular caspase 3 activity. In conclusion, SMV-loaded chitosan coated with eudragit S100 formula exhibited improved colon targeting and enhanced cytotoxicity and proapoptotic activity against HCT-116 colon cancer cells.

Optimized Conjugation of Fluvastatin to HIV-1 TAT Displays Enhanced Pro-Apoptotic Activity in HepG2 Cells.

Accumulating evidence indicates that statins reduce the risk of different cancers and inhibit the proliferation of liver cancer cells. This study aims to explore whether the electrostatic conjugation of optimized fluvastatin (FLV) to human immunodeficiency virus type 1 (HIV-1) trans-activator transcription peptide (TAT) would enhance the anti-proliferative activity against HepG2 cells. FLV-TAT conjugation was optimized to achieve the lowest size with highest zeta potential. Nine formulae were constructed, using a factorial design with three factors-FLV concentration, TAT concentration, and pH of the medium-while the responses were zeta potential and size. The optimized formula showed a particle size of 199.24 nm and 29.14 mV zeta potential. Data indicates that conjugation of FLV to TAT (optimized formula) significantly enhances anti-proliferative activity and uptake by HepG2 cells when compared to raw FLV. Flow cytometry showed significant accumulation of cells in the pre-G phase, which highlights higher apoptotic activity. Annexin V staining indicated a significant increase in total cell death in early and late apoptosis. This was confirmed by significantly elevated caspase 3 in cells exposed to FLV-TAT preparation. In conclusion, the FLV-TAT optimized formula exhibited improved anti-proliferative action against HepG2. This is partially attributed to the enhanced apoptotic effects and cellular uptake of FLV.

Icariin enhances AMP-activated protein kinase and prevents high fructose and high salt-induced metabolic syndrome in rats.

Metabolic syndrome (MetS) is an increasing health threat and often leads to cardiovascular complications. The aim of this study was to evaluate icariin's ability to combat MetS induced in rats and outline the involved mechanisms of action. Rats were grouped in four batches. The controls received a regular diet and water. MetS was induced in the remaining three groups using a high-salt high-fructose diet. Groups 1 and 2 were given daily doses of saline, while Groups 3 and 4 received 25 and 50 mg/kg icariin, respectively, for 12 weeks in total. The experimental protocol was carried out for 12 weeks consecutively. Icariin significantly decreased body mass index (BMI), adiposity index and body weight. Further, icariin protected against dyslipidemia, hyperglycemia, and hyperinsulinemia and improved insulin resistance as given by the homeostatic model assessment of insulin resistance (HOMA-IR) values. Icariin guarded against the rise in serum interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α). In addition, it significantly inhibited the decrease in mRNA expression of glucose transporter type 4 (GLUT4) and liver kinase B1 (LKB1). These effects were accompanied by decreased liver content of nuclear factor kappa B (NFκB) and enhanced serum levels of phosphorylated 5'-adenosine monophosphate-activated protein kinase (p-AMPK). Further, icariin significantly increased p-AMPK/AMPK ratio in liver tissues. Conclusively, icariin offers protection in experimentally induced MetS, partially due to AMPK activation.

Encapsulation of Lovastatin in Zein Nanoparticles Exhibits Enhanced Apoptotic Activity in HepG2 Cells.

Research on statins highlights their potent cytotoxicity against cancer cells and their potential for cancer prevention. The aim of the current study was to examine whether loading lovastatin (LVS) in zein (ZN) nanoparticles (NPs) would potentiate the anti-proliferative effects of LVS and enhance its proliferation-inhibiting activity in HepG2 cells. LVS-ZN NPs were prepared and showed excellent characteristics, with respect to their particle size, zeta potential, diffusion, and entrapment efficiency. In addition, they showed the most potent anti-proliferative activity against HepG2 cells. ZN alone showed an observable anti-proliferative that was significantly higher than that of raw LVS. Furthermore, LVS uptake by HepG2 cells was greatly enhanced by the formulation in ZN. A cell cycle analysis indicated that LVS induced a significant cell accumulation in the G2/M and pre-G phases. In this regard, the LVS-ZN NPs exhibited the highest potency. The accumulation in the pre-G phase indicated an enhanced pro-apoptotic activity of the prepared formula. The cells incubated with the LVS-ZN NPs showed the highest percentage of cells with annexin-V positive staining. In addition, the same incubations showed the highest content of caspase-3 enzyme in comparison to raw LVS or ZN. Thus, the loading of LVS in ZN nanoparticles enhances its anti-proliferative activity against HepG2 cells, which is attributed, at least partly, to the enhanced cellular uptake and the induction of apoptosis.

Phenolics Isolated from Aframomum meleguta Enhance Proliferation and Ossification Markers in Bone Cells.

Osteoporosis is a serious health problem characterized by decreased bone mineral density and deterioration of bone microarchitecture. Current antiosteoporotic agents exhibit a wide range of adverse effects; meanwhile, phytochemicals are effective and safer alternatives. In the current work, nine compounds belonging to hydroxyphenylalkane and diarylheptanoid groups were isolated from Aframomum meleguea seeds and identified as 6-gingerol (1), 6-paradol (2), 8-dehydrogingerdione (3), 8-gingerol (4), dihydro-6-paradol (5), dihydrogingerenone A (6), dihydrogingerenone C (7), 1,7-bis(3,4-dihydroxy-5-methoxyphenyl)heptane-3,5-diyl diacetate (8), and 1-(3,4-dihydroxy-5-methoxyphenyl)-7-(3,4-dihydroxyphenyl)heptane-3,5-diyl diacetate (9). The structures of isolated compounds were established by NMR and mass spectral data, in addition to referring to literature data. Exposure of MCF-7, MG-63, and SAOS-2 cells to subcytotoxic concentrations of the compounds under investigation resulted in accelerated proliferation. Among them, paradol was selected for further detailed biochemical analysis in SAOS-2 cells. DNA flowcytometric analysis of cell cycle distribution revealed that paradol did not induce any significant change in the proliferation index of SAOS-2 cells. Assessment of osteogenic gene expression revealed that paradol enhanced the expression of osteocyte and osteoblast-related genes and inhibited osteoclast and RUNX suppressor genes. Biochemically, paradol enhanced alkaline phosphatase activity and vitamin D content and decreased the osteoporotic marker acid phosphatase. In conclusion, paradol, which is a major constituents of A. melegueta seeds, exhibited potent proliferative and ossification characteristics in bone cells.

Antiproliferative effects of selected marine organisms collected from Red Sea.

Ten selected marine organisms representing different classes of marine fauna and flora were collected from Saudi Arabia territorial water. They were Antipathes dichotoma, Rumphella sp., Dictoyota dichotoma, Hyrtios erectus, Petrosia sp., Heteroxenia fuscescens, Rumphella aggregata, Sinularia polydactyla, Sarcophyton glaucum, Sarcophyton trocheliophorum. Samples were lyophilized and extracted. Their cytotoxic activity was assessed by determining their IC50's against HepG2, A549 and PC-3 cancer cell lines. The extracts showed variable activities against A549 with IC50 in the range 388.3-0.1µg/mL; HepG2 with IC50 in range 382.5-0.1µg/ml and PC-3 with IC50 in the range 428.6-0.1µg/mL. Dictoyota dichotoma, Hyrtios erectus, Rumphella aggregata and Sarcophyton glaucum exhibited the highest antiproliferative activity. Therefore, their impact on cell cycle was examined by flow cytometry technique. It was concluded that they cause G0/G1, S-phase and G2/M cell cycle arrest.

Caffeic Acid Phenethyl Ester: A Review of Its Antioxidant Activity, Protective Effects against Ischemia-reperfusion Injury and Drug Adverse Reactions.

Propolis, a honey bee product, has been used in folk medicine for centuries for the treatment of abscesses, canker sores and for wound healing. Caffeic acid phenethyl ester (CAPE) is one of the most extensively investigated active components of propolis which possess many biological activities, including antibacterial, antiviral, antioxidant, anti-inflammatory, and anti-cancer effects. CAPE is a polyphenolic compound characterized by potent antioxidant and cytoprotective activities and protective effects against ischemia-reperfusion (I/R)-induced injury in multiple tissues such as brain, retina, heart, skeletal muscles, testis, ovaries, intestine, colon, and liver. Furthermore, several studies indicated the protective effects of CAPE against chemotherapy-induced adverse drug reactions (ADRs) including several antibiotics (streptomycin, vancomycin, isoniazid, ethambutol) and chemotherapeutic agents (mitomycin, doxorubicin, cisplatin, methotrexate). Due to the broad spectrum of pharmacological activities of CAPE, this review makes a special focus on the recently published data about CAPE antioxidant activity as well as its protective effects against I/R-induced injury and many adverse drug reactions.

Influence of Onabotulinumtoxin A on testes of the growing rat.

Onabotulinumtoxin A (onabotA) is gaining wide medical use in children. The present study was planned to investigate the influence of its injection on the maturing testicular structures in rats. Immature rats were injected in the bilateral cremaster muscles by onabotA with three doses of (10, 20, and 40 U/kg) three times in a 2-week interval. The effect of these injections on fertility indices was examined. Levels of antisperm antibodies and several apoptosis parameters were also investigated. DNA content in form of ploidy and histopathological alterations were assessed. OnabotA-injected groups showed decreased sperm count and semen quality, while sperm vitality, morphology, and testosterone levels were not significantly affected. Furthermore, DNA flow cytometric analysis confirmed delayed sperm maturation. Apoptosis markers were significantly increased by the injections. In conclusion, onabotA injection in growing rats adversely affected sperm count and maturation. OnabotA testicular effects are mediated, at least partly, by apoptosis.

Antiproliferative effects of triterpenoidal derivatives, obtained from the marine sponge Siphonochalina sp., on human hepatic and colorectal cancer cells.

Three triterpenoidal derivatives [Sipholenol A (1), sipholenol L (2) and sipholenone A (3)] were isolated from the Red Sea sponge Siphonochalina sp. The structures were determined based on spectroscopic measurements (NMR, UV, IR and MS). The isolated compounds were evaluated for their cytotoxic activity against three cancer cell lines; HepG2, Caco-2 and HT-29. Moreover, the effects of these metabolites on cell cycle progression as well as cell cycle regulating proteins were assessed. Compounds 1, 2 and 3 showed moderate activity against HepG2 cells with IC(50) values of 17.18 ± 1.18, 24.01 ± 0.59 and 35.06 ± 1.10 µM, respectively. Compounds 1 and 2 exerted a considerable antiproliferative effect with IC(50) values of 4.80 ± 0.18 and 26.64 ± 0.30 µM, respectively, against Caco-2 cells. Finally, 1 and 2 exhibited antiproliferative activity against colorectal cancer cells (HT-29) with IC(50) values of 24.65 ± 0.80 and 4.48 ± 0.1 µM, respectively. Cell cycle analysis indicated that these compounds induced cell cycle arrest particularly in G0/G1 and S phases. Furthermore, the triterpenoids increased the expression of cyclin-B1, cyclin-D1 and cleaved caspase-3, as determined by immunofluorescence, indicating an important role of apoptosis in cell death induced by these compounds.

Polyphenols from Erythrina crista-galli: Structures, Molecular Docking and Phytoestrogenic Activity.

OBJECTIVES: The current study aimed at exploring the secondary metabolites content of Erythrina crista-galli aqueous methanol extract and assessing its phytoestrogenic and cytoprotective activities. METHODS: Isolation of the compounds was carried out using conventional chromatographic techniques. The structures of the isolated compounds were elucidated based on the UV, NMR spectral data along with their mass-spectrometric analyses. The phytoestrogenic activity was evaluated in-silico and in vitro using the Arabidopsis thaliana pER8: GUS reporter assay and the proliferation-enhancing activity of MCF-7 cells. KEY FINDINGS: Phytochemical investigation of E. crista-galli aqueous methanol extract resulted in the isolation and identification of five flavonoids. The plant extract and its fractions showed significant estrogenic activities compared to controls. CONCLUSION: Five flavonoids were identified from E. crista-galli aqueous methanol extract. To the best of our knowledge, among these flavonoids, apigenin-7-O-rhamnosyl-6-C-glucoside was isolated for the first time from nature. Moreover, luteolin-6-C-glucoside was isolated for the first time from this plant. The plant revealed promising phytoestrogenic activities. This gives rationale to some of its pharmacological properties and suggests additional phytoestrogenic effects, which have not been reported yet.

The effect of pomegranate fruit extract on testosterone-induced BPH in rats.

BACKGROUND: Benign prostatic hyperplasia (BPH) affects many men after the age of 50 years. Inflammation and oxidative stress along with apoptotic changes are thought to play an important role in the pathology of BPH. Pomegranate contains a variety of polyphenolic compounds that have been studied in a medley of diseases for their anti-oxidant, anti-inflammatory and pro-apoptotic properties. Therefore, this study examined the effect of Pomegranate Fruit Extract (PFE) on the development of BPH using a testosterone-induced BPH model in rats. METHODS: A total of 48 rats were randomly divided into six groups of eight, one group served as the control, BPH was induced by testosterone 3 mg/kg S.C. daily in four groups, three of them received PFE by oral gavage daily at doses of 25, 50, and 100 mg/kg respectively, while one group received PFE at a dose of 50 mg/kg without induction of BPH. RESULTS: PFE at a dose of 100 mg/kg was the most effective in decreasing testosterone-induced increase in prostate weight, prostate weight/body weight ratio, and PAP levels by 30.8%, 55%, and 68% respectively and in preventing the accompanying histological changes. In the BPH model, testosterone significantly decreased GSH, SOD, and CAT to 0.45, 0.64, and 0.88 of the control group values respectively, and significantly increased MDA by >6-fold. In combination with testosterone, PFE dosed at 100 mg/kg significantly increased GSH, SOD, and CAT to 0.83, 0.92, and 0.93 of the control group values respectively, whereas MDA was significantly decreased by 72% compared with the testosterone treated group. In addition to this, at the range of doses studied, PFE lowered COX-II, iNOS, Ki-67 expression, and increased apoptotic index. CONCLUSION: The current findings elucidate the effectiveness of PFE in preventing testosterone-induced BPH in rats. This could be attributed, at least partly, to its anti-oxidant, anti-inflammatory, and pro-apoptotic properties.

Mechanistic Evidence of Viscum schimperi (Viscaceae) Antihyperglycemic Activity: From a Bioactivity-guided Approach to Comprehensive Metabolite Profiling.

Diabetes mellitus is possibly the world's largest growing metabolic disorder. Effective treatment of diabetes is increasingly dependent on active constituents of medicinal plants capable of controlling hyperglycemia as well as its secondary complications. Viscum schimperi Engl. is a plant growing in Saudi Arabia and known for its antidiabetic activity. The potential antidiabetic activity of its methanol extract as well as its chloroform, n-butanol, and the remaining water fractions was evaluated in streptozotocin-induced diabetic rats at two dose levels. The antidiabetic activity was assessed through the determination of fasting blood glucose level, insulin levels, area under the curve (AUC) in oral glucose tolerance test, glucose absorption in isolated rat gut assay, and glucose uptake by psoas muscle. Moreover, large-scale untargeted metabolite profiling of methanol extract was performed via UPLC-PDA and qTOF-MS (ultra-performance liquid chromatography photodiode array detection and quadrupole time-of-flight mass spectrometry) respectively, to explore its chemical composition and standardization of its extract. Multivariate statistical analysis including principal component analysis and orthogonal projection to latent structures discriminant analysis was used to determine bioactives in its fractions. In conclusion, oleanane triterpenes and O-caffeoyl quinic acid conjugates were the major compounds that might account for antihyperglycemic effect of the plant.

Adverse testicular effects of Botox® in mature rats.

Botox® injections are taking a consistently increasing place in urology. Intracremasteric injections, particularly, have been applied for cryptorchidism and painful testicular spasms. Studies outlining their safety for this use are, however, scanty. Thus, the present study aimed at evaluating possible testicular toxicity of Botox® injections and their effect on male fertility. Mature rats were given intracremasteric Botox® injections (10, 20 and 40 U/kg) three times in a two-week interval. Changes in body and testes weights were examined and gonadosomatic index compared to control group. Semen quality, sperm parameters, fructose, protein, cholesterol and triglycerides contents were assessed. Effects on normal testicular function were investigated by measuring testosterone levels and changes in enzyme activities (lactate dehydrogenase-X and acid phosphatase). To draw a complete picture, changes in oxidative and inflammatory states were examined, in addition to the extent of connective tissue deposition between seminiferous tubules. In an attempt to have more accurate information about possible spermatotoxic effects of Botox®, flowcytometric analysis and histopathological examination were carried out. Botox®-injected rats showed altered testicular physiology and function. Seminiferous tubules were separated by dense fibers, especially with the highest dose. Flowcytometric analysis showed a decrease in mature sperms and histopathology confirmed the findings. The oxidative state was, however, comparable to control group. This study is the first to show that intracremasteric injections of Botox® induce adverse testicular effects evidenced by inhibited spermatogenesis and initiation of histopathological changes. In conclusion, decreased fertility may be a serious problem Botox® injections could cause.