Dissolving microneedles for alopecia treatment.

Alopecia is a treatable benign disease, however, approximately 15-30% of women and 50% of men suffer from alopecia, which greatly affects patient's self-esteem and quality of life. Currently, commercial products for alopecia treatment include topical minoxidil solution, oral finasteride tablets and oral baricitinib tablets. However, the barrier of stratum corneum, systemic adverse effects and poor cure rate limit the application of commercial products. Therefore, researchers investigated the mechanism of alopecia, and developed new drugs that could target lactate dehydrogenase-related pathways, remove excessive reactive oxygen in hair follicles, and reduce the escape of hair follicle stem cells, thus injecting new strength into the treatment of alopecia. Moreover, starting from improving drug stratum corneum penetration and reducing side effects, researchers have developed hair loss treatment strategies based on dissolved microneedles (MNs), such as drug powders/microparticles, nanoparticles, biomimetic cell membranes, phototherapy and magnetically responsive soluble microneedles, which show exciting alopecia treatment effects. However, there are still some challenges in the practical application of the current alopecia treatment strategy with soluble microneedles, and further studies are needed to accelerate its clinical translation.

Schisandra chinensis bee pollen's chemical profiles and protective effect against H2O2-induced apoptosis in H9c2 cardiomyocytes.

BACKGROUND: Schisandra chinensis (Turcz.) Baill bee pollen extract (SCBPE) is often used as a functional food in China due to its good antioxidant property. However, its chemical compositions and effects on H9c2 cardiomyocytes against H2O2-induced cell injury still lacks of reports thus far. This study aimed to characterize the main components of SCBPE and investigate its protective effects against H2O2-induced H9c2 cardiomyocyte injury. METHODS: The main components of SCBPE were analyzed via ultraperformance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-QTOF MS/MS). The three main nucleosides in SCBPE were quantitatively analyzed via ultraperformance liquid chromatography-diode array detection. Furthermore, the potential mechanism by which SCBPE exerts protective effects against H2O2-induced H9c2 cardiomyocyte injury was explored for the first time via cell survival rate measurements; cell morphological observation; myocardial superoxide dismutase (SOD) activity and malondialdehyde (MDA) and glutathione (GSH) level determination; flow cytometry; and quantitative polymerase chain reaction. RESULTS: Two carbohydrates, three nucleosides, and nine quinic acid nitrogen-containing derivatives in SCBPE were identified or tentatively characterized via UPLC-QTOF MS/MS. The nine quinic acid nitrogen-containing derivatives were first reported in bee pollen. The contents of uridine, guanosine, and adenosine were 2.4945 ± 0.0185, 0.1896 ± 0.0049, and 1.8418 ± 0.0157 µg/mg, respectively. Results of in vitro experiments showed that cell survival rate, myocardial SOD activity, and GSH level significantly increased and myocardial MDA level significantly decreased in SCBPE groups compared with those in H2O2 group. Cell morphology in SCBPE groups also markedly improved compared with that in H2O2 group. Results indicated that SCBPE protected H9c2 cardiomyocytes from H2O2-induced apoptosis by downregulating the mRNA expressions of Bax, cytochrome C, and caspase-3 and upregulating the Bcl-2 mRNA expression. CONCLUSIONS: This study is the first to report that SCBPE could protect against oxidative stress injury and apoptosis in H2O2-injured H9c2 cells. Results indicated that the nucleosides and quinic acid nitrogen-containing derivatives could be the main substances that exert protective effects against H2O2-induced H9c2 cardiomyocyte injury.

Antioxidative and Cardioprotective Effects of Schisandra chinensis Bee Pollen Extract on Isoprenaline-Induced Myocardial Infarction in Rats.

Oxidative stress plays an important role in the pathogenesis of myocardial infarction (MI). Schisandra chinensis bee pollen extract (SCBPE) possesses powerful antioxidant capacity. This study aimed to further explore the antioxidative and cardioprotective effects of SCBPE on acute MI induced by isoprenaline (ISO) in rats. The rats were intragastrically administrated with SCBPE (600, 1200, or 1800 mg/kg/day) and Compound Danshen dropping pills (270 mg/kg/day) for 30 days, then subcutaneously injected with ISO (65 mg/kg/day) on the 29th and 30th day. Compared with the model group, pretreatment with middle and high doses of SCBPE significantly reduced serum aspartate transaminase, lactate dehydrogenase, and creatine kinase activities and increased myocardial superoxide dismutase, glutathione peroxidase, and catalase activities. The histopathologic aspects showed that pathological heart change was found in the model group and reduced to varying degrees in the SCBPE groups. Moreover, the protein expression of nuclear factor-erythroid 2-related factor 2 (Nrf-2), heme oxygenase-1 (HO-1), and Bcl2 in the heart increased in the SCBPE groups, while that of Bax decreased compared to the model group. Besides this, uridine was isolated from S. chinensis bee pollen for the first time. This study could provide a scientific basis for using Schisandra chinensis bee pollen as a functional food for the prevention of MI.

Anti-hypertensive and cardioprotective effects of a novel apitherapy formulation via upregulation of peroxisome proliferator-activated receptor-α and -γ in spontaneous hypertensive rats.

Ventricular remodeling is associated with many heart diseases, and ventricular remodeling induced by hypertension can be fatal independent of hypertension. In this study, we prepared a novel apitherapy formulation, designated Bao-Yuan-Ling (BYL), which contained propolis, royal jelly, and bee venom, to treat spontaneous hypertensive rats (SHRs). We then evaluated the pharmacology of BYL and the potential mechanisms through which BYL affects hypertension and ventricular remodeling. We found that BYL treatment could reduce blood pressure in SHRs. Thereafter, we found that BYL treatment reduced serum levels of angiotensin II, endothelin 1, and transforming growth factor-ß and improved the myocardial structure. Moreover, the results of quantitative real-time polymerase chain reaction indicated that BYL treatment could upregulate the mRNA expression of peroxisome proliferator-activated receptor (PPAR)-α and PPAR-γ. Thus, we could conclude that BYL had hypotensive and cardioprotective effects in SHRs, potentially through improvement of myocardial energy metabolism.

Protective effect of Schisandra chinensis bee pollen extract on liver and kidney injury induced by cisplatin in rats.

Cisplatin (CP) has been used to cure numerous forms of cancers effectively in clinics, however, it could induce some toxic effects. Bee pollen is a natural compound, produced by honey bees. It is obtained from collected flower pollen and nectar, mixed with bee saliva. Bee pollen produced from Schisandra chinensis plants is described to exert potent antioxidant effects and to be a free radical scavenger. The purpose of this study was to investigate the effects of therapeutic treatment with Schisandra chinensis bee pollen extract (SCBPE) on liver and kidney injury induced by CP. The rats were intragastrically administrated with different doses of SCBPE (400mg/kg/day, 800mg/kg/day, 1200mg/kg/day) and vitamin C (400mg/kg/day, positive control group) for 12days, and the liver and kidney injury models were established by single intraperitoneal injection of CP (8mg/kg) at seventh day. The effect of SCBPE on CP toxicity was evaluated by measuring markers of liver and kidney injury in serum, levels of lipid peroxidation and antioxidants in liver and kidney, observing pathological changes of tissue, and quantified expression of NFκB, IL-1ß, IL-6, cytochrome C, caspase3, caspase9, p53 and Bax in liver and kidney. Compared with the model group, the activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and the content of blood urea nitrogen (BUN), creatinine (Cr) in serum all decreased in SCBPE high dose group. Meanwhile, the activities of superoxide dismutase (SOD), catalase (CAT) and the content of reduced glutathione (GSH) in liver and kidney increased, and the content of malondialdehyde (MDA) and inducible nitric oxide synthase (iNOS) decreased. In addition, the histopathologic aspects showed that the pathological changes of liver and kidney were found in the model group, and SCBPE group reduced to varying degrees. Moreover, the expression of NFκB, IL-1ß, IL-6, cytochrome C, caspase3, caspase9, p53 and Bax in liver and kidney decreased. Therefore, SCBPE could reduce the damage of liver and kidney caused by CP by reducing the level of oxidative stress, and improving the antioxidant, anti-inflammatory and anti-apoptotic capacity of the body.

Zebrafish: A promising in vivo model for assessing the delivery of natural products, fluorescence dyes and drugs across the blood-brain barrier.

The blood brain barrier (BBB) is the network of capillaries that controls the passage of substances from the blood into the brain and other parts of the central nervous system (CNS). As this barrier is the major obstacle for drug delivery into CNS, a credible BBB model is very necessary to assess the BBB permeability of novel neuroactive compounds including thousands of bioactive compounds which have been extracted from medicinal plants and have the potential for the treatment of CNS diseases. Increasing reports indicated that zebrafish has emerged as a timely, reproducible model for BBB permeability assessment. In this review, the development and functions of the BBB in zebrafish, such as its anatomical morphology, tight junctions, drug transporters and enzyme expression, are compared with those in mammals. The studies outlined in this review describe the utilization of the zebrafish as a BBB model to investigate the permeability and distribution of fluorescent dyes and drugs. Particularly, this review focuses on the use of zebrafish to evaluate the delivery of natural products and nanosized drug delivery systems across the BBB. Due to the highly conserved nature of both the structure and function of the BBB between zebrafish and mammals, zebrafish has the potential to be developed as a model for assessing and predicting the permeability of BBB to novel compounds.

Soxhlet-assisted matrix solid phase dispersion to extract flavonoids from rape (Brassica campestris) bee pollen.

Soxhlet-assisted matrix solid phase dispersion (SA-MSPD) method was developed to extract flavonoids from rape (Brassica campestris) bee pollen. Extraction parameters including the extraction solvent, the extraction time, and the solid support conditions were investigated and optimized. The best extraction yields were obtained using ethanol as the extraction solvent, silica gel as the solid support with 1:2 samples to solid support ratio, and the extraction time of one hour. Comparing with the conventional solvent extraction and Soxhlet method, our results show that SA-MSPD method is a more effective technique with clean-up ability. In the test of six different samples of rape bee pollen, the extracted content of flavonoids was close to 10mg/g. The present work provided a simple and effective method for extracting flavonoids from rape bee pollen, and it could be applied in the studies of other kinds of bee pollen.

Chinese Medicine in Inhalation Therapy: A Review of Clinical Application and Formulation Development.

Chinese medicine (CM) in inhalation therapy has a long history of applications since ancient China in the forms of smoke, steam vapor, medicated pillows and aromatic sachets. Over the years, thousands of clinical treatments involving the inhalation of CMs have been reported for the treatment of respiratory disease. Shuanghuanglian, Yuxingcao and Qingkailing are primarily applied in pneumonia and bronchitis. At present, metered dose inhalation (MDI), aromatic inhalation and nebulized inhalation are used extensively in practice. In particular, nebulized CM for the treatment of respiratory diseases has been applied as a noninvasive route with reduced serious adverse reactions and is equivalent to or more efficacious than its intravenous counterparts. Although nebulized CM is widely used in clinical practice, only three MDI and five aromatic inhalations of CM products have been approved by the China Food and Drug Administration (CFDA), and no products in the form of a dry powder inhaler (DPI) or in dosage forms intended for nebulization have been reported. The development of formulations for CM has focused on improving the aerodynamic performance of the particles prepared by spray drying, enhancing the bioavailability and local concentration in the respiratory tract, and increasing the mucoadhesion and sustained release of the CM upon the incorporation of novel excipients. New devices, including MDI and nebulizer devices, have been developed for the delivery of the above-mentioned particles to the pulmonary system. Although the development of CM inhalation products to meet the international quality standards is facing a number of challenges, the inhalation of CMs show great potential for further exploration, particularly as an alternative route to IV infusion for the treatment of respiratory diseases.

Honey reduces blood alcohol concentration but not affects the level of serum MDA and GSH-Px activity in intoxicated male mice models.

BACKGROUND: For a long time, honey was purportedly helpful to prevent drunkenness and relieve hangover symptoms. However, few of the assertions have experienced scientific assessment. The present study examined the effects of honey on intoxicated male mice. METHODS: Low or high doses of lychee flower honey (2.19 or 4.39 g/kg body weight, respectively) were single orally administrated 30 min before the ethanol intoxication of mice, followed by recording the locomotor activity by autonomic activity instrument and observing the climbing ability after alcohol. On the other hand, 2.19 g/kg honey was single orally administrated 5 min after the ethanol intoxication of mice, followed by determining the ethanol concentration in mice blood. In addition, subacute alcoholism mice models were developed and after the treatment of 2.19 g/kg honey s.i.d for successive three days, the level of serum malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) activity were detected in the models. RESULTS: Both of the two doses of honey increased the autonomic activity of alcoholized mice. Furthermore, the treatment of 2.19 g/kg honey could decrease significantly the blood ethanol concentration in intoxicated mice. The anti-intoxication activity of honey could be due to the effect of the fructose contained in the honey. Meanwhile, honey could not affect the serum MDA level and GSH-Px activity in alcoholism mice models. CONCLUSION: Honey indeed possesses anti-intoxication activity.

Comparative sucrose responsiveness in Apis mellifera and A. cerana foragers.

In the European honey bee, Apis mellifera, pollen foragers have a higher sucrose responsiveness than nectar foragers when tested using a proboscis extension response (PER) assay. In addition, Africanized honey bees have a higher sucrose responsiveness than European honey bees. Based on the biology of the Eastern honey bee, A. cerana, we hypothesized that A. cerana should also have a higher responsiveness to sucrose than A. mellifera. To test this hypothesis, we compared the sucrose thresholds of pollen foragers and nectar foragers in both A. cerana and A. mellifera in Fujian Province, China. Pollen foragers were more responsive to sucrose than nectar foragers in both species, consistent with previous studies. However, contrary to our hypothesis, A. mellifera was more responsive than A. cerana. We also demonstrated that this higher sucrose responsiveness in A. mellifera was not due to differences in the colony environment by co-fostering two species of bees in the same mixed-species colonies. Because A. mellifera foragers were more responsive to sucrose, we predicted that their nectar foragers should bring in less concentrated nectar compared to that of A. cerana. However, we found no differences between the two species. We conclude that A. cerana shows a different pattern in sucrose responsiveness from that of Africanized bees. There may be other mechanisms that enable A. cerana to perform well in areas with sparse nectar resources.