The azole biocide climbazole induces oxidative stress, inflammation, and apoptosis in fish gut.

Climbazole is an azole biocide that has been widely used in formulations of personal care products. Climbazole can cause developmental toxicity and endocrine disruption as well as gut disturbance in aquatic organisms. However, the mechanisms behind gut toxicity induced by climbazole still remain largely unclear in fish. Here, we evaluate the gut effects by exposing grass carp (Ctenopharyngodon idella) to climbazole at levels ranging from 0.2 to 20 µg/L for 42 days by evaluating gene transcription and expression, biochemical analyses, correlation network analysis, and molecular docking. Results showed that climbazole exposure increased cyp1a mRNA expression and ROS level in the three treatment groups. Climbazole also inhibited Nrf2 and Keap1 transcripts as well as proteins, and suppressed the transcript levels of their subordinate antioxidant molecules (cat, sod, and ho-1), increasing oxidative stress. Additionally, climbazole enhanced NF-κB and iκBα transcripts and proteins, and the transcripts of NF-κB downstream pro-inflammatory factors (tnfα, and il-1ß/6/8), leading to inflammation. Climbazole increased pro-apoptosis-related genes (fadd, bad1, and caspase3), and decreased anti-apoptosis-associated genes (bcl2, and bcl-xl), suggesting a direct reaction to apoptosis. The molecular docking data showed that climbazole could form stable hydrogen bonds with CYP1A. Mechanistically, our findings suggested that climbazole can induce inflammation and oxidative stress through CYP450s/ROS/Nrf2/NF-κB pathways, resulting in cell apoptosis in the gut of grass carp.

Global research status of localised scleroderma reported over the period 1993-2022: A 30-year bibliometric analysis.

Localised scleroderma predominantly affects the skin with an unknown aetiology. Despite its clinical importance, no comprehensive bibliometric analysis has been conducted to assess the existing research landscape and future prospects for localised scleroderma. The articles related to localised scleroderma were retrieved from the WoSCC database and analysed by VOSviewer 1.6.10.0 (Leiden University, Netherlands), CiteSpace 6.1.R1 (Dreiser University, USA), and HistCite 2.1 (New York, United States). 2049 research papers pertaining to localised scleroderma spanning the years from 1993 to 2022 were extracted from the WoSCC database. The United States exhibited the highest productivity with 644 papers, accounting for 31.43% of the total output, followed by Germany with 206 papers (10.05%) and Italy with 200 papers (9.76%). Regarding academic institutions and journals, the University of Texas System and Dermatology published the most significant number of papers, and Professor Ihn, H emerged as the most prolific contributor among scholars. The top 10 cited references primarily concentrated on the diagnosis and treatment of localised scleroderma. "Phototherapy" and "methotrexate (MTX)" surfaced as the most recent and noteworthy keywords, representing the research hotspots in the domain of localised scleroderma. This bibliometric analysis furnishes valuable insights into the contemporary research landscape of localised scleroderma.

Chemical fingerprint analysis and quality assessment of Tibetan medicine Triphala from different origins by high-performance liquid chromatography.

INTRODUCTION: Although the Tibetan medicine Triphala (THL) is widely used in many countries, insufficient progress has been made in quality control. OBJECTIVES: The present study aimed to propose a methodology for quality control of THL based on HPLC fingerprinting combined with an orthogonal array design. METHODS: Seven identified peaks were used as indicators to examine the effects of temperature, extraction time, and solid-liquid ratio on the dissolution of active ingredients in THL. Fingerprint analysis was performed on 20 batches of THL from four geographical areas (China, Laos, Thailand, and Vietnam). For further chemometric assessment, analysis techniques including similarity analysis, hierarchical clustering analysis, principal component analysis, and orthogonal partial least squares discrimination analysis (OPLS-DA) were used to classify the 20 batches of samples. RESULTS: Fingerprints were established and 19 common peaks were identified. The similarity of 20 batches of THL was more than 0.9 and the batches were divided into two clusters. Four differential components of THL were identified based on OPLS-DA, including chebulinic acid, chebulagic acid, and corilagin. The optimal extraction conditions were an extraction time of 30 min, a temperature of 90°C, and a solid-liquid ratio of 30 mL/g. CONCLUSION: HPLC fingerprinting combined with an orthogonal array design could be used for comprehensive evaluation and quality assessment of THL, providing a theoretical basis for further development and utilization of THL.

Research progress on effects of traditional Chinese medicine on myocardial ischemia-reperfusion injury: A review.

Ischemic heart disease (IHD) is a high-risk disease in the middle-aged and elderly population. The ischemic heart may be further damaged after reperfusion therapy with percutaneous coronary intervention (PCI) and other methods, namely, myocardial ischemia-reperfusion injury (MIRI), which further affects revascularization and hinders patient rehabilitation. Therefore, the investigation of new therapies against MIRI has drawn great global attention. Within the long history of the prevention and treatment of MIRI, traditional Chinese medicine (TCM) has increasingly been recognized by the scientific community for its multi-component and multi-target effects. These multi-target effects provide a conspicuous advantage to the anti-MIRI of TCM to overcome the shortcomings of single-component drugs, thereby pointing toward a novel avenue for the treatment of MIRI. However, very few reviews have summarized the currently available anti-MIRI of TCM. Therefore, a systematic data mining of TCM for protecting against MIRI will certainly accelerate the processes of drug discovery and help to identify safe candidates with synergistic formulations. The present review aims to describe TCM-based research in MIRI treatment through electronic retrieval of articles, patents, and ethnopharmacology documents. This review reported the progress of research on the active ingredients, efficacy, and underlying mechanism of anti-MIRI in TCM and TCM formulas, provided scientific support to the clinical use of TCM in the treatment of MIRI, and revealed the corresponding clinical significance and development prospects of TCM in treating MIRI.

[Two new triterpeneoids from roots of Dolomiaea souliei].

The present study analyzed the chemical constituents in dried roots of Dolomiaea souliei. Chromatographic methods, such as normal-phase, and reversed-phase column chromatography, TLC, and preparative HPLC, were applied to separate and purify the petroleum ether extract of D. souliei. The structures of the purified constituents were identified by multiple spectroscopic methods including 1 D NMR, 2 D NMR, IR, UV, and HR-ESI-MS. Fourteen triterpenoids were obtained and identified as bauer-8-ene-3,11-dione-7α-ol(1), bauer-8-ene-3-one-7α,11α-diol(2), 3-oxo-11α-hydroxy-urs-12-ene(3), 3-oxour-12-ene-1ß,11α-diol(4), 3ß,11α-dihydroxy-urs-12-ene(5), taraxast-20-ene-3ß,30-diol(6), 28-hydroxy-3-oxo-12-ursene(7), 3ß-hydroxytaraxast-20-ene-30-aldehyde(8), urs-12-ene-2α,3ß,28-triol(9), 20-hydroxylupan-3-one(10), monogynol A(11), obtusalin(12), 3-oxo, 11α-hydroxy-olean-12-ene(13), and isocabralealactone(14). Among them, compounds 1 and 2 were new compounds. Compounds 4-10, 12, and 14 were isolated from this genus for the first time. Compounds 3 and 11 were obtained from D. souliei for the first time.

Laser Speckle Contrast Imaging for the Objective Assessment of Blood Perfusion in Keloids Treated With Dual-Wavelength Laser Therapy.

BACKGROUND: Most of the widely used methods for the assessment of keloid treatment are subjective grading scales based on the opinion of an individual clinician or patient. There is a growing need for objective methods to evaluate keloid treatment. OBJECTIVE: This study aimed to evaluate the value of laser speckle contrast imaging (LSCI) as an objective method for the assessment of dual-wavelength laser therapy for keloids. METHODS: This prospective study included 21 patients with 54 keloids. All patients were treated with a combined 585-nm pulsed dye laser and 1,064 nm neodymium-doped yttrium aluminum garnet dual-wavelength laser at 4 weeks to 6 weeks intervals. Keloids were assessed using the Vancouver Scar Scale (VSS) and LSCI. RESULTS: The total VSS score significantly decreased after 4 sessions of treatment (p < .05). Blood perfusion in keloids as measured by LSCI was significantly reduced after treatment (p < .05). The improvement of chest keloids in terms of the total VSS score and blood perfusion was significantly greater than that of scapular keloids (p < .05). There was a positive correlation between decreased perfusion and reduced total VSS score (R2 = 0.84). CONCLUSION: Blood perfusion in keloids significantly decreased after dual-wavelength laser therapy. Laser speckle contrast imaging is a promising objective method for assessing the improvement of keloids treated with laser therapy.

Mandibular osteomyelitis after hyaluronic acid injection.

BACKGROUND: Mandibular osteomyelitis after filler injection is extremely rare. AIMS: We reported a case of mandibular osteomyelitis after hyaluronic acid injection. PATIENTS: A 33-year-old woman received 1 mL hyaluronic acid injection on her chin 1 year ago, after which her chin kept swelling and painful, and gradually ulcerated with pus flowing out. She received antibiotics, debridement procedures, negative pressure wound therapy, and hyperbaric oxygen therapy without symptoms improved. Cone-beam computed tomography scan showed local bone destruction, sequestrum formation, and tissue calcification on the right mandible body. The patient was diagnosed with mandibular osteomyelitis and received local curettage for the removal of necrotized bone. RESULTS: Literature search found no case reports on mandibular osteomyelitis after filler injection so far. CONCLUSION: Minimizing the risk of contamination and infection is strictly required during the filler injection process. Once the patient shows signs of incurable mandibular infection postoperation, clinicians should consider the possibility of osteomyelitis.

Association between Selenium in Soil and Diabetes in Chinese Residents Aged 35-74 Years: Results from the 2010 National Survey of Chronic Diseases and Behavioral Risk Factors Surveillance.

OBJECTIVE: To explore the association between soil selenium levels and the risk of diabetes in Chinese adults aged 35-74 years. METHODS: Data for this study were derived from the China Chronic Diseases and Behavioral Risk Factors Surveillance 2010 survey. Selenium concentrations in soil were obtained from the Atlas of Soil Environmental Background Values in China. A two-level binary logistic regression model was used to determine the association between soil selenium concentrations and the risk of diabetes, with participants nested within districts/counties. RESULTS: A total of 69,332 participants aged 35-74 years, from 158 districts/counties were included in the analysis. Concentrations of selenium in soil varied greatly across the 158 districts/counties, with a median concentration of 0.219 mg/kg ( IQR: 0.185-0.248). The results showed that both Quartile 1 (0.119-0.185 mg/kg) and Quartile 4 (0.249-0.344 mg/kg) groups were positively associated with diabetes compared to a soil selenium concentration of 0.186-0.219 mg/kg (Quartile 2), crude odds ratios ( ORs) (95% CI) were 1.227 (1.003-1.502) and 1.280 (1.048-1.563). The P values were 0.045 and 0.013, for Quartile 1 and Quartile 4 groups, respectively. After adjusting for all confounding factors of interest, the Quartile 1 group became non-significant, and the Quartile 4 group had an adjusted OR (95% CI) of 1.203 (1.018-1.421) relative to the reference group (Quartile 2), the P values was 0.030. No significant results were seen for the Quartile 3 group (0.220-0.248 mg/kg) compared to the reference group. CONCLUSION: Excessive selenium concentrations in soil could increase the risk of diabetes among Chinese adults aged 35-74 years.

Superior hypoglycemic activity of mulberry lacking monosaccharides is accompanied by better activation of the PI3K/Akt and AMPK signaling pathways.

Mulberry has been used as a functional food to treat type 2 diabetes mellitus (T2DM). However, it contains relatively high levels of fructose and glucose, which are not suitable for excess consumption by diabetic patients. In this study we used microbial fermentation to remove fructose and glucose from mulberry fruit, and then determined the effects on glycemia, the phosphatidylinositol 3-hydroxykinase/Akt (PI3K/Akt) and adenosine monophosphate-activated protein kinase (AMPK) signaling pathways and their downstream effectors in T2DM mice. After 5 weeks of administration, fermented mulberry (FM) significantly reduced fasting blood glucose, and also improved insulin sensitivity and glucose tolerance, more effectively than unfermented mulberry (MP). Moreover, compared with MP, FM had a more marked effect on the protein expression of intermediates in the PI3K/Akt and AMPK signaling pathways and their effectors: insulin receptor, phosphorylated Akt (Ser 308), phosphorylated glycogen synthase kinase-3ß (Ser 9), glycogen synthetase, phosphorylated forkhead transcription factor 1 (Ser 256), pyruvate carboxylase, phosphoenolpyruvate carboxykinase, fructose-1, 6-bisphosphatase, glucose-6-phosphatase, lipoprotein lipase, and phosphorylated AMPK (Thr 172), glucose transporter 4 and pyruvate kinase. These findings indicate that mulberry fruit modified to remove fructose and glucose may be more promising than whole mulberry as a treatment for diabetes.

Nanoemulsion improves hypoglycemic efficacy of berberine by overcoming its gastrointestinal challenge.

Berberine (BBR) is an important natural product with poor gastrointestinal behavior includes low permeability, P-glycoprotein efflux, and mass elimination in the intestine. The aim of this study was to develop a novel nanoemulsion (NE) to improve the hypoglycemic efficacy of BBR. NE was prepared and characterized by morphology and droplet size detection, stored stability, in vitro intestinal lipolysis and metabolism, Caco-2 cells transport, in situ single-pass intestinal perfusion, oral bioavailability in rats, and hypoglycemic efficacy in high-fat diet and streptozocin-induced mice. BBR-loaded NE exhibits small droplet size (30.56 ±â€¯0.35 nm) and good stability. NE could remain intact after lipolysis and protect BBR against the intestinal metabolism mediated by CYP2D6 and CYP3A4. Cells transport and intestinal perfusion studies revealed that NE decreases the P-glycoprotein efflux of BBR by 2-fold and enhances its permeability by 5.5-fold. Consequently, NE increased the oral bioavailability of BBR in rats by 212.02%. Compared to BBR control, blood glucose level of diabetic mice by NE was decreased by 3-fold. This novel NE provides a promising carrier to improve the hypoglycemic efficacy of BBR by overcoming its gastrointestinal deficiency, which may offer a product for the therapy of diabetes.

A regulatory mutant on TRIM26 conferring the risk of nasopharyngeal carcinoma by inducing low immune response.

The major histocompatibility complex (MHC) is most closely associated with nasopharyngeal carcinoma (NPC), but the complexity of its genome structure has proven challenging for the discovery of causal MHC loci or genes. We conducted a targeted MHC sequencing in 40 Cantonese NPC patients followed by a two-stage replication in 1065 NPC cases and 2137 controls of Southern Chinese descendent. Quantitative RT-PCR analysis (qRT-PCR) was used to detect gene expression status in 108 NPC and 43 noncancerous nasopharyngeal (NP) samples. Luciferase reporter assay and chromatin immunoprecipitation (ChIP) were used to assess the transcription factor binding site. We discovered that a novel SNP rs117565607_A at TRIM26 displayed the strongest association (OR = 1.909, Pcombined = 2.750 × 10-19 ). We also observed that TRIM26 was significantly downregulated in NPC tissue samples with genotype AA/AT than TT. Immunohistochemistry (IHC) test also found the TRIM26 protein expression in NPC tissue samples with the genotype AA/AT was lower than TT. According to computational prediction, rs117565607 locus was a binding site for the transcription factor Yin Yang 1 (YY1). We observed that the luciferase activity of YY1 which is binding to the A allele of rs117565607 was suppressed. ChIP data showed that YY1 was binding with T not A allele. Significance analysis of microarray suggested that TRIM26 downregulation was related to low immune response in NPC. We have identified a novel gene TRIM26 and a novel SNP rs117565607_A associated with NPC risk by regulating transcriptional process and established a new functional link between TRIM26 downregulation and low immune response in NPC.

Research progress on berberine with a special focus on its oral bioavailability.

The natural product berberine (BBR) has become a potential drug in the treatment of diabetes, hyperlipidemia, and cancer. However, the oral delivery of BBR is challenged by its poor bioavailability. It is necessary to improve the oral bioavailability of BBR before it can be used in many clinical applications. Understanding the pharmacokinetic characteristics of BBR will enable the development of suitable formulas that have improved oral bioavailability. The key considerations for BBR are how to enhance the drug absorption and to avoid the intestinal first-pass effect. This review summarizes the pharmacological activities of BBR and analyzes the factors that lead to its poor oral bioavailability. In particular, the therapeutic potential of BBR in new indications from the aspect of oral bioavailability is discussed. In conclusion, BBR is a promising drug candidate for metabolic disorders and cancer but faces considerable challenges due to its poor oral bioavailability.

Two new triterpenoids from Gypsophila oldhamiana.

Two new triterpenoids (1-2) were isolated and elucidated from the roots of Gypsophila oldhamiana, together with four known triterpenoids (3-6). Their structures were identified to be 3ß-hydroxyolean-13(18)-ene-23, 28-dioic acid (1), 3ß, 12α-dihydroxy-23-carboxyolean-28, 13ß-olide (2), 3ß, 16α-dihydroxy-23-oxoolean-13(18)-en-28-oic acid (3), gypsogenin (4), quillaic acid (5) and gypsogenic acid (6) by spectral methods. All compounds were tested for their cytotoxicities against human tumour cell lines (lung cancer H460 and gastric cancer SGC-7901) and for their antiangiogenic effects using a zebra fish model. All compounds showed interesting antiangiogenic activities and the significant cytotoxicities against H460.

[Preparation and Dissolution Evaluation of Breviscapine Self-microemulsion].

OBJECTIVE: To study the prescription and preparation technology of breviscapine self-microemulsion for oral administration, and to evaluate the quality, stability and in vitro dissolution. METHODS: The prescription and preparation technology were selected and optimized through the solubility experiment, compatibility test, and pseudo-ternary phase diagram method, using the self-emulsifying time, appearance, particle diameter and stability as indexes. The droplet morphous, drug content, stability and dissolution were evaluated. Results:The prescription composition of breviscapine self-microemulsion was caprylic/capric triglyceride(GTCC,40%), Cremophor RH-40(50%), and PEG-400 (10%), with the drug loading of 7. 0 mg/g. The breviscapine self-microemulsion exhibited uniform and transparent,with the particle size of 38. 57 nm,Zeta potential of - 8. 80 mV. The results of dissolution indicated that the accumulative dissolution in 0. 1 mol/L hydrochloric acid was able to reach 90. 30% after 90 min, being 5. 9 times to that of the raw material medicine. The stability result showed that the content of breviscapine self-microemulsion was affected by high temperature, indicating it should be stored at low temperature. CONCLUSION: The preparation of breviscapine self-microemulsion is simple, which can increase the solubility of breviscapine in water and the absorption of breviscapine in the stomach and intestine, and conform to the main indexes of oral drug delivery system. It offers the basis for further research of breviscapine.

Lobelia chinensis: chemical constituents and anticancer activity perspective.

Research has demonstrated that many chemical constituents dominated by piperidine alkaloids and flavonoids, such as lobelanidine, lobeline, and lobelanine, have been obtained from Lobelia chinensis Lour. Experimental studies and clinical applications have also indicated that L. chinensis possesses a number of pharmacological activities (e.g., diuretic, choleretic, breathing excitement, anti-venom, anti-bacterial, and anticancer). This paper focuses on the properties, chemical constituents, and anticancer activity of L. chinensis to clarify the connection among them, and identify the active anticancer compounds. This work serves as the foundation for further research and development of L. chinensis.

[Comparison of seed oil physicochemical characteristics among three cultivars of Jatropha curcas L].

Taking the cultivars Nanyou 1, 2, and 3 of barbadosnut (Jatropha curcas L. ) with different genotypes that can grow and seed normally at the inshore land in Hainan as test materials, the characters of their seeds and the physicochemical characteristics of their seed oils were analyzed and compared. No significant differences were observed in the seed length, width, thickness, and surface area among the cultivars, but Nanyou 2 had greater 1000 seed mass and lower unsound kernel percentage than Nanyou 1 and Nanyou 3, suggesting that the seed satiation of Nanyou 2 was good and the fecundity was excellent. The kernel oil content of Nanyou 3 was significantly higher than that of Nanyou 1 and Nanyou 2, and there was no significant difference between Nanyou 1 and Nanyou 2. The seed oil peroxide value, refractive index, and saponification value of the three cultivars had no significant differences, but the acid value for Nanyou 2 was much lower than that for Nanyou 1 and Nanyou 3. The seed oil iodine value of the three cultivars was all below 100, and was significantly lower for Nanyou 2 than for Nanyou 1 and Nanyou 3. The fatty acids in the three cultivars seed oils were mainly oleic acid, palmitic acid, linoleic acid, stearic acid, and margaric acid, and dominated by unsaturated fatty acids. The contents of saturated fatty acids in Nanyou 2 seed oil were relatively higher than those in Nanyou 1 and Nanyou 3 seed oils, indicating that comparing with Nanyou 1, cultivars Nanyou 2 and Nanyou 3 had relatively good potential for application.

Comparison of ancient and modern Clonorchis sinensis based on ITS1 and ITS2 sequences.

In 1975, an ancient corpse buried in 167 BC was found at Jiangling County, Hubei Province of China. The eggs of Clonorchis sinensis found in the gall bladder of the corpse were preserved well. In the present paper, we extracted the genomic DNA from the ancient eggs and modern eggs, respectively, and the internal transcribed spacer 1 and 2 (ITS1 and ITS2) at ribosomal RNA genes were studied. The results show that ITS2 sequences from the ancient sample were identical with those from modern samples, but in ITS1 differences in 15 nucleotide positions were found between the ancient and modern samples. The results demonstrated that it is possible to extract and sequence DNA from ancient parasite eggs. The ITS1 sequence obtained differed from all modern ones available to date. This might indicate sequence divergence through time, or might reflect a sequence polymorphism that may eventually be found also in modern samples.

[Preparation and in vitro evaluations of topically applied capsaicin transfersomes].

OBJECTIVE: Capsaicin transfersomes were prepared and its quality specifications were evaluated. METHOD: Capsaicin transfersomes were prepared by high shear dispersing machine and evaluated on the entrapment efficiency, drugs release rate and in vitro skin permeation. RESULT: Capsaicin transfersomes is composed of single unilamellar vesicles, with average size of 150.6 nm. Capsaicin entrapment efficiency achieved 96.7% while concentration of lecithin used was 8%. cumulative release amount of capsaicin was in direct proportion to the ethanol concentration in the medium. The in vitro rate cumulative penetration rate of capsaicin was higher in transfersomes than in cream and suspension in rats. Adomen skin cumulative penetration rate in vitro of capsaicin transfersomes in mouse was significantly higher than that from rat and men. In the same way,cumulative penetration rate in vitro of capsaicin transfersomes through abdomen skin epidermal membrance was significantly higher than that with derma and full skin in men. CONCLUSION: Entrapment efficiency of capsaicin transfersomes reached 96.7%, meeting the criterion of China pharmacopia( > 80%), skin penetration of capsaicin was enhanced by a capsaicin transfersomes preparation and was affected by diverse characters and levels of skin.

[Determination of capsaicin in Pheretima aspergillum from different habitats by RP-HPLC].

OBJECTIVE: To determine the content of hypoxanthine in Pheretima aspergillum from different habitats. METHOD: A RP-HPLC method was established. The chromatographic column was Inertsil ODS-EP. The mobile phase was H2O-CH3OH-C4H8O(93:: 7: 0.05). The flow rate was 1.0 ml/min, and the detection wavelength was 254 nm. RESULTS: The average recoveries for hypoxanthine was 98.6% , precision of the method was 0. 50% (RSD, n = 6). CONCLUSION: The method can be used to determine the content of hypoxanthine in Pheretima aspergillum from diffrent habitats.

Preparation and in vitro and in vivo evaluations of topically applied capsaicin transfersomes / 药学学报

<p><b>AIM</b>To prepare capsaicin transfersomes and evaluate them in vitro and in vivo.</p><p><b>METHODS</b>Capsaicin transfersomes were prepared by high shear dispersing machine and evaluated by entrapment efficiency, release rate, in vitro skin permeation and distribution in different tissues in vivo.</p><p><b>RESULTS</b>Capsaicin transfersomes were composed of single unilamellar vesicles with an average diameter of 150.6 nm. Capsaicin entrapment efficiency increased distinctly with increasing of concentration of lecithin and entrapment efficiency is 96.7% while concentration of lecithin to 8%. Cumulative release amount of capsaicin is in direct proportion to the ethanol concentration in the receptor medium. In vitro capsaicin cumulative penetration amount showed higher levels in transfersomes than cream and suspension in rat abdominal skin. Abdominal skin cumulative penetration amount in vitro of capsaicin transfersomes in mouse was significantly higher than that from rat and men. In the same way, abdominal skin epidermal membrane cumulative penetration amount in vitro of capsaicin transfersomes was significantly higher than that from derma and full skin in human abdominal skin. The capsaicin tissue distribution of capsaicin injection by multiple celiac injections in rats is different: bone > plasma > skin > muscle. There is a similar result by multiple thigh topical application of capsaicin transfersomes: bone > skin > plasma > muscle.</p><p><b>CONCLUSION</b>Entrapment efficiency of capsaicin transfersomes reached the criterion of China Pharmacopoeia (> 80%) and capsaicin skin penetration can be increased by capsaicin transfersomes. It should be noted that the diverse characters and levels of skin may probably affect the permeating capability of capsaicin. Capsaicin tissue distribution in bone and muscle is similar and is different in plasma and skin by multiple injections and topical skin apply.</p>