Photobiomodulation Can Prevent Medication-Related Osteonecrosis of the Jaw Formation in Tooth Extraction Site of Rat Model.

Objective: This study aims to explore the preventive potential of photobiomodulation (PBM) in bisphosphonate-related osteonecrosis of the jaw (BRONJ) using a rat model. Methods: An experimental rat model was established, exposing rats to zoledronic acid (ZA), a primary risk factor for BRONJ. An 810 nm diode laser was applied with parameters of 0.33 W/cm2 power density and 10 J/cm2 energy density for 30 sec. PBM was initiated 1 day pre-extraction and continued for 2 weeks. The impact of PBM on wound healing in both soft and hard tissues was evaluated post tooth extraction. Results: ZA exposure hindered wound healing in both soft and hard tissues after tooth extraction. PBM intervention effectively mitigated the adverse effects of ZA, promoting healing processes in both tissue types. This suggests the potential of PBM as a preventive strategy for BRONJ in patients on long-term bisphosphonate treatment. Moreover, PBM exhibited enhanced wound healing in normal rats, indicating its broader applicability beyond BRONJ cases. Conclusions: PBM shows promise in preventing and improving wound healing in BRONJ and normal cases. These findings underscore the significance of optimizing PBM parameters and suggest its potential clinical relevance as a preventive intervention for BRONJ and a promoter of wound healing.

Effect of Blueberry Supplementation on a Diet-Induced Rat Model of Prediabetes-Focus on Hepatic Lipid Deposition, Endoplasmic Stress Response and Autophagy.

Blueberries, red fruits enriched in polyphenols and fibers, are envisaged as a promising nutraceutical intervention in a plethora of metabolic diseases. Prediabetes, an intermediate state between normal glucose tolerance and type 2 diabetes, fuels the development of complications, including hepatic steatosis. In previous work, we have demonstrated that blueberry juice (BJ) supplementation benefits glycemic control and lipid profile, which was accompanied by an amelioration of hepatic mitochondrial bioenergetics. The purpose of this study is to clarify the impact of long-term BJ nutraceutical intervention on cellular mechanisms that govern hepatic lipid homeostasis, namely autophagy and endoplasmic reticulum (ER) stress, in a rat model of prediabetes. Two groups of male Wistar rats, 8-weeks old, were fed a prediabetes-inducing high-fat diet (HFD) and one group was fed a control diet (CD). From the timepoint where the prediabetic phenotype was achieved (week 16) until the end of the study (week 24), one of the HFD-fed groups was daily orally supplemented with 25 g/kg body weight (BW) of BJ (HFD + BJ). BW, caloric intake, glucose tolerance and insulin sensitivity were monitored throughout the study. The serum and hepatic lipid contents were quantified. Liver and interscapular brown and epidydimal white adipose tissue depots (iBAT and eWAT) were collected for histological analysis and to assess thermogenesis, ER stress and autophagy markers. The gut microbiota composition and the short-chain fatty acids (SCFAs) content were determined in colon fecal samples. BJ supplementation positively impacted glycemic control but was unable to prevent obesity and adiposity. BJ-treated animals presented a reduction in fecal SCFAs, increased markers of arrested iBAT thermogenesis and energy expenditure, together with an aggravation of HFD-induced lipotoxicity and hepatic steatosis, which were accompanied by the inhibition of autophagy and ER stress responses in the liver. In conclusion, despite the improvement of glucose tolerance, BJ supplementation promoted a major impact on lipid management mechanisms at liver and AT levels in prediabetic animals, which might affect disease course.

Anti-rheumatoid arthritis potential of different fractions derived from of Coluria longifolia.

Coluria longifolia Maxim (C. longifolia) is a Chinese folk medication commonly used to treat arthritis and joint pain. Literatures have reported that C. longifolia has significant anti-inflammatory, analgesic and antipyretic effects. The aim of this research was to assay the effective fractions of C. longifolia (EFCL) against rheumatoid arthritis (RA) and to elucidate its anti-RA mechanism on a preliminary basis. The rat model of collagen-induced arthritis (CIA) was established. The therapeutic effects of different fractions in vivo were evaluated by body weight changes, a foot swelling score, inflammatory factors and histopathological examination. The mechanism of EFCL was investigated by activity of oxidative stress related enzyme, qPCR and Western blotting tests. In vivo results showed that total extraction (TE) and n-butanol fraction (NF) could significantly alleviate the symptoms of RA, decrease the levels of IL-6 and TNF-α (P < 0.01), and improve histopathological injury. The mechanism study showed that SOD level was significantly increased with MDA level decreased in the NF group. The upregulated proteins and mRNA expression levels of Nrf2, HO1 and NQO1 after TE and NF administration suggested that the anti-arthritic effect may be related to the Nrf2 signaling pathway and downstream HO1 and NQO1. In conclusion, this study confirmed that C. longifolia is capable of treating RA with NF as the main effective fraction. Its anti-RA action may be associated with Nrf2 signaling pathway and downstream HO1 and NQO1.

Effects of Guizhi and Erxian Decoction on menopausal hot flashes: insights from the gut microbiome and metabolic profiles.

AIMS: To examine the influence of GED on the gut microbiota and metabolites using a bilateral ovariectomized (OVX) rat model. We tried to elucidate the underlying mechanisms of GED in the treatment of menopausal hot flashes. METHODS AND RESULTS: 16S rRNA sequencing, metabonomics, molecular biological analysis, and fecal microbiota transplantation (FMT) were conducted to elucidate the mechanisms by which GED regulates the gut microbiota. GED significantly reduced OVX-induced hot flashes and improved disturbances in the gut microbiota metabolites. Moreover, FMT validated that the gut microbiota can trigger hot flashes, while GED can alleviate hot flash symptoms by modulating the composition of the gut microbiota. Specifically, GED upregulated the abundance of Blautia, thereby increasing l(+)-ornithine levels for the treatment of menopausal hot flashes. Additionally, GED affected endothelial nitric oxide synthase and heat shock protein 70 (HSP70) levels in the hypothalamic preoptic area by changing the gut microbiota composition. CONCLUSIONS: Our study illuminated the underlying mechanisms by which GED attenuated the hot flashes through modulation of the gut microbiota and explored the regulatory role of the gut microbiota on HSP70 expression in the preoptic anterior hypothalamus, thereby establishing a foundation for further exploration of the role of the gut-brain axis in hot flashes.

Advantage of ostarine over raloxifene and their combined treatments for muscle of estrogen-deficient rats.

PURPOSE: Selective androgen (ostarine, OST) and estrogen (raloxifene, RAL) receptor modulators with improved tissue selectivity have been developed as alternatives to hormone replacement therapy. We investigated the combined effects of OST and RAL on muscle tissue in an estrogen-deficient rat model of postmenopausal conditions. METHODS: Three-month-old Sprague Dawley rats were divided into groups: (1) untreated non-ovariectomized rats (Non-OVX), (2) untreated ovariectomized rats (OVX), (3) OVX rats treated with OST, (4) OVX rats treated with RAL, (5) OVX rats treated with OST and RAL. Both compounds were administered in the diet. The average dose received was 0.6 ± 0.1 mg for OST and 11.1 ± 1.2 mg for RAL per kg body weight/day. After thirteen weeks, rat activity, muscle weight, structure, gene expression, and serum markers were analyzed. RESULTS: OST increased muscle weight, capillary ratio, insulin-like growth factor 1 (Igf-1) expression, serum phosphorus, uterine weight. RAL decreased muscle weight, capillary ratio, food intake, serum calcium and increased Igf-1 and Myostatin expression, serum follicle stimulating hormone (FSH). OST + RAL increased muscle nucleus ratio, uterine weight, serum phosphorus, FSH and luteinizing hormone and decreased body and muscle weight, serum calcium. Neither treatment changed muscle fiber size. OVX increased body and muscle weight, decreased uterine weight, serum calcium and magnesium. CONCLUSION: OST had beneficial effects on muscle in OVX rats. Side effects of OST on the uterus and serum electrolytes should be considered before using it for therapeutic purposes. RAL and RAL + OST had less effect on muscle and showed endocrinological side effects on pituitary-gonadal axis.

Maca roots: A potential therapeutic in the management of metabolic disorders through the modulation of metabolic biochemical markers in rats fed high-fat high-carbohydrate diet.

ETHNOPHARMACOLOGICAL RELEVANCE: Maca root (Lepidium meyenii Walp.) is a Peruvian plant of the Brassicaceae family. Maca roots are popular food supplements used to treat a variety of ailments described traditionally as enhancing metabolic and health conditions. AIM OF THE STUDY: Metabolic syndrome (MetS) has been the real scourge globally, affecting more than one-fourth of the global population. MetS causes the development of multi-organ illnesses, including altered blood cholesterol and sugar levels, oxidative stress, and hypertension. This study evaluated maca root total methanolic extract (MTE) as a potential nutraceutical to manage the complications of MetS. MATERIALS AND METHODS: After the first 4 weeks of a high-fat high-carbohydrate diet (HFCD), streptozotocin (STZ) was injected in Wistar rats to induce the MetS model. Animals were treated orally with MTE at 100 mg/kg and 300 mg/kg for 4 weeks compared to metformin at 200 mg/kg after confirmation of diabetes. RESULTS: One month of MTE supplementation in HFCD-fed rats remarkably decreased the elevation of blood glucose and lipids, improved liver function and insulin resistance, additionally it successfully restored the state of inflammatory and oxidative stress. The extract was standardized to contain total phenolics equal to 24.45 ± 0.96 µg Gallic acid/mg extract. CONCLUSIONS: Our findings suggest that MTE improves MetS by reducing hyperglycemia, hyperlipidemia, inflammation, and oxidative stress. While also improving beta cell secretory functions, implying that MTE could be used as a balancing drug in the prevention and treatment of metabolic abnormalities linked to type 2 diabetes.

Ultrastructural changes of vascular smooth muscle cells and resistance to vasospasm treatment in femoral arteries of an arteriosclerotic rat model.

The objective of this study was to establish an animal model of arteriosclerosis for assessing vasospasm and to investigate the relationship between arteriosclerosis and vasospasm. Twelve-week-old male Sprague-Dawley rats were fed a diet supplemented with adenine and vitamin D (adenine/vitD). Body weight, blood, and femoral artery histopathology were assessed at 2, 4, and 6 weeks. Change in the femoral artery was examined by transmission electron microscope (TEM). Vasospasm was induced by administering epinephrine extravascularly into the femoral artery and released by the treatment with lidocaine as a vasodilator. During this period, the extravascular diameter and blood flow were measured. The rats in the adenine/vitD group developed renal dysfunction, uremia, hyperphosphatemia, and elevated serum alkaline phosphatase. Histological and TEM analyses of the femoral arteries in the treated rats revealed the degeneration of elastic fibers and extensive calcification of the tunica media and intima. Vascular smooth muscles were degenerated and osteoblasts were developed, resulting in calcified arteriosclerosis. Vasospasm in arteriosclerotic arteries was detected; however, vasodilation as well as an increase in the blood flow was not observed. This study revealed the development of vasospasm in the femoral arteries of the arteriosclerotic rats and, a conventional vasodilator did not release the vasospasm.

Anti-inflammatory, antioxidant, antiangiogenic, and therapeutic efficacy of neroli oil in rats with endometriotic lesions.

INTRODUCTION: Endometriosis is a serious health problem among women of reproductive age, with pelvic pain and infertility. Given the limited success of current treatments, this study explores Neroli oil (N.O.) effects on inflammation, oxidation, angiogenesis, and tissue remodeling implicated in endometriosis. MATERIALS AND METHODS: Albino Wistar female rats were used to simulate an endometriosis model. Groups were established for comparison: a control, an endometriosis model, a N.O.-treated group, and a N.O.-treated group postendometriosis induction. The study focused on Tumor necrosis factor-alpha (TNF-α), Interleukin 6, Interleukin 8, vascular endothelial growth factor (VEGF), myeloperoxidase, Matrix metalloproteinase-1 (MMP-1), nitric oxide, superoxide dismutase, catalase, and anti-mullerian hormone values, as well as histopathological evaluations of endometriotic foci. RESULTS: AMH values showed a significant increase in the endometriosis group treated with N.O. compared with the endometriosis group (p < 0,01).A statistically significant decrease was found in MMP-1 level in the endometriosis group that underwent N.O. (p < 0.001). Increased CAT (p < 0.0001) and decrease in nitric oxide (p < 0.01) are found in N.O.-treated endometriosis group. TNF-α levels in the endometriosis group showed a statistically significant increase in the endometriosis group when compared with the control and sham group (p < 0.001, p < 0.01 respectively). In our study, a statistically significant increase was observed in VEGF levels (p < 0.001) in endometriosis group and significant decrease in the N.O. administered endometriosis model group. Groups treated with N.O. showed decreased inflammation and congestion scores. Histopathological assessments demonstrated reduced inflammation and tissue remodeling signs in endometriotic foci. CONCLUSION: This study highlights the potential of N.O. in the treatment of endometriosis, owing to its anti-inflammatory, antioxidant, and antiangiogenic properties that can disrupt chronic processes. Our findings lend support to utilization of herbal remedies for the management of endometriosis, thereby emphasizing the necessity for additional comprehensive investigations in the future.

Effects of Gender and Vitamin D on Vascular Reactivity of the Carotid Artery on a Testosterone-Induced PCOS Model.

The negative cardiovascular effects of polycystic ovary syndrome (PCOS) and vitamin D deficiency (VDD) have been discussed previously; however, the sex differences between PCOS females and males are not yet known. Our aim was to investigate the effect of PCOS and VDD in the carotid artery of male and female Wistar rats. Females were treated with transdermal testosterone (Androgel) for 8 weeks, which caused PCOS. VDD and vitamin D supplementation were accomplished via diet. The carotid arteries' contraction and relaxation were examined using myography. Receptor density was investigated using immunohistochemistry. In PCOS females, angiotensin receptor density, angiotensin II-induced contraction, androgen receptor optical density, and testosterone-induced relaxation increased. The increased contractile response may increase cardiovascular vulnerability in women with PCOS. As an effect of VDD, estrogen receptor density increased in all our groups, which probably compensated for the reduced relaxation caused by VDD. Testosterone-induced relaxation was decreased as a result of VDD in males and non-PCOS females, whereas this reduction was absent in PCOS females. Male sex is associated with increased contraction ability compared with non-PCOS and PCOS females. VDD and Androgel treatment show significant gender differences in their effects on carotid artery reactivity. Both VDD and PCOS result in a dysfunctional vascular response, which can contribute to cardiovascular diseases.

The Cavernous Nerve Injury Rat Model: A Pictorial Essay on Post-Radical Prostatectomy Erectile Dysfunction Research.

Understanding and addressing post-radical prostatectomy (RP) erectile dysfunction (ED) is of paramount importance for clinicians. Cavernous nerve (CN) injury rat model studies have provided consistently promising experimental data regarding regaining erectile function (EF) after nerve damage-induced ED. However, these findings have failed to translate efficiently into clinical practice, with post-RP ED therapeutic management remaining cumbersome and enigmatic. This disparity highlights the need for further standardization and optimization of the elaborate surgical preparation protocols and multifaceted reporting parameters involved in reliable CN injury rat model experimentation. Even so, despite its technical complexity, this animal model remains instrumental in exploring the functional implications of RP, i.e., surgical lesions of the neurovascular bundles (NVBs). Herein, besides cavernous nerve (CN) dissection, injury, and electrostimulation, multiple pressure measurements, i.e., mean arterial pressure (MAP) and intra-cavernosal pressure (ICP), must also be achieved. A transverse cervical incision allows for carotid artery cannulation and MAP measurements. Conversely, ICP measurements entail circumcising the penis, exposing the ischiocavernous muscle, and inserting a needle into the corporal body. Finally, using an abdominal incision, the prostate is revealed, and the major pelvic ganglia (MPG) and CNs are dissected bilaterally. Specific surgical techniques are used to induce CN injuries. Herein, we provide a narrative and illustrative overview regarding these complex experimental procedures and their particular requirements, reflecting on current evidence and future research perspectives.

Hepatoprotective effects of bioactive compounds from traditional herb Tulsi (Ocimum sanctum Linn) against galactosamine-induced hepatotoxicity in rats.

Ocimum sanctum L. (Tulsi; Family: libiaceae), also known as "The Queen of herbs" or "Holy Basil," is an omnipresent, multipurpose plant that has been used in folk medicine of many countries as a remedy against several pathological conditions, including anticancer, antidiabetic, cardio-protective, antispasmodic, diaphoretic, and adaptogenic actions. This study aims to assess O. sanctum L.'s hepatoprotective potential against galactosamine-induced toxicity, as well as investigate bioactive compounds in each extract and identify serum metabolites. The extraction of O. sanctum L as per Ayurveda was simultaneously standardized and quantified for biochemical markers: rutin, ellagic acid, kaempferol, caffeic acid, quercetin, and epicatechin by HPTLC. Hepatotoxicity was induced albino adult rats by intra-peritoneal injection of galactosamine (400 mg/kg). The quantified hydroalcoholic and alcoholic extract of O. sanctum L (100 and 200 mg/kg body weight/day) were compared for evaluation of hepatoprotective potential, which were assessed in terms of reduction in histological damage, change in serum enzymes such as AST, ALT, ALP and increase TBARS. Twenty chemical constituents of serum metabolites of O. sanctum were identified and characterized based on matching recorded mass spectra by GC-MS with those obtained from the library-Wiley/NIST. We evaluated the hepatoprotective activity of various fractions of hydroalcoholic extracts based on the polarity and investigated the activity at each phase (hexane, chloroform, and ethyl acetate) in vitro to determine how they affected the toxicity of CCL4 (40 mM) toward Chang liver cells. The ethyl acetate fraction of the selected plants had a higher hepatoprotective activity than the other fractions, so it was used in vacuum liquid chromatography (VLC). The ethyl acetate fraction contains high amounts of rutin (0.34% w/w), ellagic acid (2.32% w/w), kaempferol (0.017% w/w), caffeic acid (0.005% w/w), quercetin (0.038% w/w), and epicatechin (0.057% w/w) which are responsible for hepatoprotection. In comparison to standard silymarin, isolated bioactive molecules displayed the most significant hepatoprotective activity in Chang liver cells treated to CCl4 toxicity. The significant high hepatoprotection provided by standard silymarin ranged from 77.6% at 100 µg/ml to 83.95% at 200 µg/ml, purified ellagic acid ranged from 70% at 100 µg/ml to 81.33% at 200 µg/ml, purified rutin ranged from 63.4% at 100 µg/ml to 76.34% at 200 µg/ml purified quercetin ranged from 54.33% at 100 µg/ml to 60.64% at 200 µg/ml, purified epicatechin ranged from 53.22% at 100 µg/ml to 65.6% at 200 µg/ml, and purified kaempferol ranged from 52.17% at 100 µg/ml to 60.34% at 200 µg/ml. These findings suggest that the bioactive compounds in O. sanctum L. have significant protective effects against galactosamine-induced hepatotoxicity.

Anti Inflammatory Action of Allium Sativum Ethanol Extract to Prevent Lung Damage in Smoker Rat Model.

Background: Smoking is the leading cause of death in worldwide and is known as one of the risk factors in the development and pathogenesis of several diseases and most are respiratory and cardiovascular diseases. Secondhand smoke (SHS) exposure is associated with negative health consequences including respiratory tract infection, asthma, and cancer. One of the pathogenesis that has known to cause these diseases is inflammation. Garlic (Allium sativum) is a medicinal herb that contains Allicin and other active constituents that are known to have anti-inflammatory ability by suppressing the expression and production of proinflammatory cytokines that will cause inflammation. Objective: The aim of this study is; to analyze the anti-inflammatory action of Allium sativum ethanol extract to prevent lung damage in the smoker rat model. Methods: This is a case-control study with five groups of rats each group contains of three rats. The five groups were negative control (KN), 10 days (10d) smoker (K1), 20 days (20d) smoker (K2), 20d smoker treated with Allium sativum for 10 days (K3) and 20d smoker treated with Allium sativum for 20 days (K4). After 20 days all animals were sacrificed and histological preparation of lung organs was observed under a microscope with 100 dan 400 times magnification and then captured by photomicrograph for analyzed. Results: There were improvements in lung structure both in group K3 and K4 . there was a decrease of leucocytes and inflammatory cells infiltration that covered almost all alveolar surface to 10-20% surface area and the dilated alveoli decrease from more than 50% to less than 30% area. The bronchus was clean in both two groups compared to the groups that were not treated with Allium sativum. Conclusion: This study shows that Allium sativum ethanol extract has the ability to prevent lung damage in the smoker rat model.

Effects of ligandrol as a selective androgen receptor modulator in a rat model for osteoporosis.

INTRODUCTION: The selective androgen receptor modulator ligandrol (LGD-4033 or VK5211) has been shown to improve muscle tissue. In the present study, the effect of ligandrol on bone tissue was investigated in ovariectomized rat model. MATERIALS AND METHODS: Three-month-old Sprague Dawley rats were either ovariectomized (OVX, n = 60) or left intact (NON-OVX, n = 15). After 9 weeks, OVX rats were divided into four groups: untreated OVX (n = 15) group and three OVX groups (each of 15 rats) treated with ligandrol orally at doses of 0.03, 0.3, or 3 mg/kg body weight. After five weeks, lumbar vertebral bodies (L), tibiae, and femora were examined using micro-computed tomographical, biomechanical, ashing, and gene expression analyses. RESULTS: In the 3-mg ligandrol group, bone structural properties were improved (trabecular number: 38 ± 8 vs. 35 ± 7 (femur), 26 ± 7 vs. 22 ± 6 (L), 12 ± 5 vs. 6 ± 3 (tibia) and serum phosphorus levels (1.81 ± 0.17 vs.1.41 ± 0.17 mmol/l), uterus (0.43 ± 0.04 vs. 0.11 ± 0.02 g), and heart (1.13 ± 0.11 vs. 1.01 ± 0.08 g) weights were increased compared to the OVX group. Biomechanical parameters were not changed. Low and medium doses did not affect bone tissue and had fewer side effects. Body weight and food intake were not affected by ligandrol; OVX led to an increase in these parameters and worsened all bone parameters. CONCLUSION: Ligandrol at high dose showed a subtle anabolic effect on structural properties without any improvement in biomechanical properties of osteoporotic bones. Considering side effects of ligandrol at this dose, its further investigation for the therapy of postmenopausal osteoporosis should be reevaluated.

Intraperitoneal BromAc® Does Not Interfere with the Healing of Colon Anastomosis.

A combination of bromelain and acetylcysteine, BromAc®, is an efficient intraperitoneal mucolytic for thick mucus secreted in pseudomyxoma peritonei (PMP). Patients with PMP quite often undergo colon anastomosis. Hence, we investigated the effect of the intraperitoneal delivery of BromAc® on colon-anastomosis healing in a rat model. Sixteen Wistar rats were divided into two groups (N = 8). The controls received intraperitoneal saline after anastomosis, whilst the other group received BromAc®. They were monitored for body-weight and general health parameters. Half the rats in each group (N = 4) were culled at 4 or 13 days post-surgery for assessment. The healing process of the tissues was assessed by burst pressure and collagen density with histology to assess the integrity of the internal organs. The results indicated that there was a similar pattern of weight fluctuation during the experiment, although the rats treated with the BromAc® showed slightly greater weight loss during the first 4 days. Although the burst pressure was similar in both groups, the BromAc® group at day 13 showed a slightly higher burst pressure, which was complemented by a higher collagen density (albeit not statistically significant). The histology of the internal organs was comparable to those of the controls. This study indicates that the intraperitoneal delivery of BromAc® in a rat model does not interfere with the healing process of colonic anastomosis.

Polyphenol-based targeted therapy for oral submucous fibrosis.

Oral submucous fibrosis (OSF) is a chronic, progressive, and precancerous condition mainly caused by chewing areca nut. Currently, OSF therapy includes intralesional injection of corticosteroids with limited therapeutic success in disease management. Therefore, a combined approach of in silico, in vitro and in vivo drug development can be helpful. Polyphenols are relatively safer than other synthetic counterparts. We used selected polyphenols to shortlist the most suitable compound by in silico tools. Based on the in silico results, epigallocatechin-3-gallate (EGCG), quercetin (QUR), resveratrol, and curcumin had higher affinity and stability with the selected protein targets, transforming growth factor beta-1 (TGF-ß1), and lysyl oxidase (LOX). The efficacy of selected polyphenols was studied in primary buccal mucosal fibroblasts followed by in vivo areca nut extract induced rat OSF model. In in vitro studies, the induced fibroblast cells were treated with EGCG and QUR. EGCG was safer at higher concentrations and more efficient in reducing TGF-ß1, collagen type-1A2 and type-3A1 mRNA expression than QUR. In vivo studies confirmed that the EGCG hydrogel was efficient in improving the disease conditions compared to the standard treatment betamethasone injection with significant reduction in TGF-ß1 and collagen concentrations with increase in mouth opening. EGCG can be considered as a potential, safer and efficient phytomolecule for OSF therapy and its mucoadhesive topical formulation help in the improvement of patient compliance without any side effects. Highlights Potential polyphenols were shortlisted to treat oral submucous fibrosis (OSF) using in silico tools Epigallocatechin 3-gallate (EGCG) significantly reduced TGF-ß1 and collagen both in vitro and in vivo EGCG hydrogel enhanced antioxidant defense, modulated inflammation by reducing TGF-ß1 and improved mouth opening in OSF rat model.

Profiling GABA(A) Receptor Subunit Expression in the Hippocampus of PMDD Rat Models Based on TCM Theories.

γ-Aminobutyric acid type A receptors (GABAARs) play an important role in cognitive and emotional regulation and are related to the hippocampus. However, little is known regarding patterns of hippocampal GABAAR subunit expression in rat models of premenstrual dysphoric disorder (PMDD). This study investigated the above changes by establishing two PMDD rat models based on Traditional Chinese Medicine (TCM) theories, namely, PMDD liver-qi invasion syndrome (PMDD-LIS) and PMDD liver-qi depression syndrome (PMDD-LDS). Behavioral tests were used to detect depression and irritability emotion. Western blot analysis was used to investigate protein levels of GABAAR α1, α2, α4, α5, ß2, ß3, and δ subunits, whereas ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) analysis was performed to determine gamma-aminobutyric acid (GABA) and glutamate (Glu) levels in the hippocampus across each group. Concurrently, behavioral data indicated that the PMDD-LDS and PMDD-LIS rat models had been successfully established. GABAAR α2, α5, ß2, and δ subunit was significantly upregulated, whereas α4 was significantly downregulated (P < 0.05) in PMDD-LDS rat models relative to controls. On the other hand, GABAAR α1, α2, and ß3 were significantly downregulated while α4 and ß2 were significantly upregulated in PMDD-LIS rat models relative to the control group (P < 0.05). Moreover, GABA levels significantly decreased, while Glu and the ratio of glutamate to GABA increased in PMDD-LIS rat models (P < 0.05). Conversely, GABA and Glu levels significantly decreased, whereas the ratio of glutamate to GABA increased in PMDD-LIS rat models (P < 0.05). Conclusively, our results revealed differential expression of GABAAR α1, α2, α4, α5, ß2, ß3, and δ subunits between PMDD-LIS and PMDD-LDS rat models, suggesting that they may be biomarkers in the pathogenesis of PMDD.

Quality marker discovery of Danggui Jianzhong decoction for treating primary dysmenorrhoea based on chinmedomics strategy.

BACKGROUND: Danggui Jianzhong Decoction (DGJZD) has been proven as an effective classical prescription for clinically treating primary dysmenorrhoea (PD). However, the industrialisation development and drug innovation of DGJZD remain limited due to its undefined effective constituents and quality markers (Q-markers). PURPOSE: Elucidating the Q-markers of DGJZD, which is related to clinical efficacy. METHODS: In accordance with chinmedomics strategy, we evaluated the therapeutic efficacy of DGJZD on the basis of the metabolomic profile and biomarker of a PD rat model to further identify the constituents of DGJZD in vivo that originated from the formula under the acting condition of DGJZD. The potential effective constituents and Q-markers were identified by mining the dynamic relation between the constituents in vivo and the biomarkers. RESULTS: Subsequently, 29 serum metabolites were characterized as biomarkers for PD, and DGJZD adjusted the levels of the primary biomarkers involved in arachidonic acid metabolism, glycerophospholipid metabolism, tryptophan metabolism as well as the synthesis of steroid hormones. Under the active condition of DGJZD, 20 prototype ingredients and 4 metabolites of DGJZD were found in vivo, five of which were mostly related with the efficacy of PD, namely, ferulic acid, zizyphusin, cinnamic acid, protocatechuic acid-3-glucoside, and azelaic acid. They were the potential pharmacodynamic constituents for treating PD, and they could be regarded as the Q-markers of DGJZD. CONCLUSION: Taken together, the Q-markers of DGJZD identified in this research are credible and assist in solving problems related to quality control and drug innovation, accelerating industrialisation development. Besides, the efficacy, mechanism and active ingredients of DGJZD for the treatment of PD were innovatively elucidated for the first time on the basis of the chinmedomics strategy for uncovering the Q-markers of drugs from the system perspective.

Liver regeneration after portal vein embolization: comparison between absolute ethanol and N-butyl-cyanoacrylate in an in vivo rat model.

PURPOSE: To compare the effects of absolute ethanol (ethanol) and N-butyl-cyanoacrylate (NBCA) on non-embolized liver lobe regeneration in a rat model. METHODS: Twenty-seven Sprague-Dawley rats underwent portal vein embolization (PVE) using ethanol:lipiodol, 1:1 (ethanol group, n = 11, 40.74%), NBCA:lipiodol, 1:1 (NBCA group, n = 11, 40.74%), or sham treatment (sham group, n = 5, 18.52%). The non-embolized and embolized lobe-to-whole liver weight ratios 14 days after PVE were compared among the groups (n = 5, 18.52%). The expressions of CD68 and Ki-67 and embolized-lobe necrotic area percentages one day after PVE were compared between the ethanol (n = 3, 11.11%) and NBCA (n = 3, 11.11%) groups. RESULTS: The non-embolized lobe-to-whole liver weight ratio after PVE was significantly higher in the NBCA group (n = 5, 33.33%) than in the ethanol group (n = 5, 33.33%) (84.28% ± 1.53% vs. 76.88% ± 4.12%, P = 0.029). The embolized lobe-to-whole liver weight ratio after PVE was significantly lower in the NBCA group than in the ethanol group (15.72% ± 1.53% vs. 23.12% ± 4.12%, P = 0.029). The proportions of CD68- and Ki-67-positive cells in the non-embolized lobe after PVE were significantly higher in the NBCA group (n = 30, 50%) than in the ethanol group (n = 30, 50%) [60 (48-79) vs. 55 (37-70), P = 0.003; 1 (0-2) vs. 1 (0-2), P = 0.004]. The embolized-lobe necrotic area percentage after PVE was significantly larger in the NBCA group (n = 30, 50%) than in the ethanol group (n = 30, 50%) [29.46 (12.56-83.90%) vs. 16.34 (3.22-32.0%), P < 0.001]. CONCLUSION: PVE with NBCA induced a larger necrotic area in the embolized lobe and promoted greater non-embolized liver lobe regeneration compared with PVE with ethanol.

Optimal timing of free total rhubarb anthraquinones on immune regulation in rats with severe acute pancreatitis.

ETHNOPHARMACOLOGICAL RELEVANCE: Rhubarb is the peeled and dried root of Rheum palmatum L., Rheum tanguticum Maxim. ex Balf. or Rheum officinale Baill. Free total rhubarb anthraquinones (FTRAs) isolated and extracted from rhubarb display the beneficial effects of anti-inflammation and immunological modulation. The timing of immune regulation is a major problem in the immunotherapy for severe acute pancreatitis (SAP). several studies reported that FTRAs could reduce systemic inflammatory responses by inhibiting early immune overactivity in the gut in rats with SAP. But, the optimal timing of rhubarb and FTRAs administration is not clear in clinical practice. Therefore, the time window for the best efficacy of rhubarb and FTRAs in the treatment of SAP patients should be further elucidated. AIM OF THE STUDY: The main purpose of the present study was to evaluate the efficacy and optimal timing of immune modulation with FTRAs in the treatment of SAP in rats. MATERIALS AND METHODS: FTRAs (22.5, 45 and 90 mg/kg), Rhubarb (RHU) (900 mg/kg, positive control) or normal saline (vehicle control) were initiated at 0 (immediately), 48 and 72 h every 12 h for three times in total. The therapeutic effects of FTRAs and RHU on pancreas and intestinal tissues injury, secondary infection with pseudomonas aeruginosa (PA), amylase, lipase, D-lactic acid (DLA), endotoxin (ET), proinflammatory and anti-inflammatory cytokines, macrophages, dendritic cells and regulatory T cells (Tregs) in the blood, small intestine and/or mesenteric lymph node (MLN) were determined in rats with SAP after treatment. RESULTS: The results showed that administration of FTRAs at 0 h was superior to 48 h and 72 h, which significantly protected the injury of pancreas and intestinal tissues, reduced the mortality induced by secondary infection with PA, decreased the levels of amylase, lipase, DLA, ET, tumor necrosis factor α (TNF-α), interleukin 1ß (IL-1ß), IL-6, IL-8, IL-18 and Tregs, and increased the levels of IL-4, sTNF-αR, macrophages and dendritic cells, secretary immunoglobulin A (SIgA) in the blood and/or small intestinal tissues in rats with SAP. CONCLUSIONS: In conclusion, our studies indicate that the treatment window of FTRAs for SAP is within 48 h of development, administration of FTRAs at the early stage (0 h, immune overreaction period) was the optimal time and superior to that of 48 h and 72 h for its therapeutic efficacy. The earlier the administration of FTRAs, the better the therapeutic efficacy. Therefore, our data may provide a scientific rationale for the clinical application and optimal timing of FTRAs in the treatment of SAP.

Allopregnanolone-mediated GABAA-Rα4 function in amygdala and hippocampus of PMDD liver qi-invasion syndrome model rats.

BACKGROUND: Premenstrual dysphoric disorder (PMDD) is a common mental health challenge among women of reproductive age. Allopregnanolone (3α, 5α-THP; ALLO) mediated functional alterations of GABAA receptors (GABAA-R) are involved in PMDD pathogenesis, however, the specific mechanism remains unknown. Therefore, we investigated the role of ALLO mediated GABAA-Rα4 in the pathophysiology of PMDD. PURPOSE: We determined whether the pathogenesis of PMDD is associated with ALLO mediated GABAA-Rα4 expression changes in different brain regions. METHODS: Rat models of PMDD liver-qi invasion syndrome (PMDD-LIS) were established via the resident intruder paradigm. Behavioral changes of rats were assessed by aggressive behavior tests, EPM and OFT. The levels of progesterone and ALLO in serum as well as brain areas were determined by ELISA. Variations in GABAA-Rα4 levels in brain regions were assessed by immunofluorescence and RT-PCR. Medicated serum was used to interfere with rat hippocampal neurons, and changes in Cl- current were recorded through electrophysiology. RESULTS: Premenstrual anxiety and irritability of PMDD-LIS patients can be simulated in PMDD-LIS rat models. Exogenous ALLO significantly improved the anxiety behaviors of PMDD-LIS rats. Changes in ALLO among different brain regions varied. GABAA-Rα4 expressions were low in the amygdala and abnormally high in the hippocampus, however, ALLO alleviated these deviations. Whole-cell patch clamp recording technique showed a weaker Cl- current intensity of PMDD-LIS rats, reduced neuroinhibitory functions and increased Cl- current intensity in the ALLO group drug serum intervention and enhanced emotional inhibition function. CONCLUSION: We established that ALLO regulation of the GABAA-Rα4 subunit in the amygdala and hippocampus is involved in PMDD-LIS pathogenesis.