Pilose Antler Research Articles

Pilose Antler Protein Relieves UVB-Induced HaCaT Cells and Skin Damage.

Extended exposure to UVB (280-315 nm) radiation results in oxidative damage and inflammation of the skin. Previous research has demonstrated that pilose antler extracts have strong anti-inflammatory properties and possess antioxidant effects. This study aimed to elucidate the mechanism of pilose antler protein in repairing photodamage caused by UVB radiation in HaCaT cells and ICR mice. Pilose antler protein (PAP) was found to increase the expression of type I collagen and hyaluronic acid in HaCaT cells under UVB irradiation while also inhibiting reactive oxygen species (ROS) production and oxidative stress in vitro. In vivo, the topical application of pilose antler protein effectively attenuated UVB-induced skin damage in ICR mice by reducing interleukin-1β (IL-β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) and inhibiting skin inflammation while alleviating UVB-induced oxidative stress. It was shown that pilose antler protein repaired UVB-induced photodamage through the MAPK and TGF-β/Smad pathways.

Pilose antler extracts promotes hair growth in androgenetic alopecia mice by activating hair follicle stem cells via the AKT and Wnt pathways.

Background: Angrogenetic alopecia (AGA) is one of the most prevalent hair loss disorders worldwide. The hair follicle stem cell (HFSC) is closely related to the formation of hair follicle (HF) structure and HF self-renewal. The activation of HFSC in AGA is critical for hair growth. Pilose antler has been reported to have hair growth-promoting activity, but the mechanism of action on AGA and HFSC has not been reported. Methods: We previously extracted an active component from the pilose antler known as PAEs. In this study, we conducted experiments using AGA mice and HFSC. The effects of PAEs on hair growth in AGA mice were firstly detected, and then the mechanisms of PAEs for AGA were predicted by integrating network pharmacology and de novo transcriptomics data of pilose antler. Finally, biological experiments were used to validate the molecular mechanism of PAEs in treating AGA both in vivo and in vitro. Results: It was found that PAEs promoted hair regrowth by accelerating the activation of anagen, delaying the anagen-catagen transition. It also alleviated the morphological changes, such as hair shortening, thinning, miniaturization, and HF number reduction, and regulated the hair regeneration process of four subtypes of hair. We further found that PAEs could promote the proliferation of HFSC, outer root sheath (ORS) cells, and hair bulb cells in AGA mice. We then integrated network pharmacology and pilose antler transcriptomics data to predict that the mechanism of PAEs treatment in AGA mice is closely related to the PI3K-AKT/Wnt-β-Catenin pathways. Subsequently, it was also verified that PAEs could activate both pathways in the skin of AGA mice. In addition, we found that PAEs perhaps increased the number of blood vessels around dermal papilla (DP) in experiments in vivo. Meanwhile, the PAEs stimulated the HFSC proliferation in vitro and activated the AKT and Wnt pathways. However, the proliferative activity of HFSC was inhibited after blocking the Wnt pathway and AKT activity. Conclusion: This study suggests that the hair growth-promoting effect of PAEs in AGA mice may be closely related to the stimulation of the AKT and Wnt pathways, which in turn activates the proliferation of HFSC.

Hybridization alters red deer gut microbiome and metabolites.

The host genes play a crucial role in shaping the composition and structure of the gut microbiome. Red deer is listed as an endangered species by the International Union for the Conservation of Nature, and its pilose antlers have good medicinal value. Hybridization can lead to heterosis, resulting in increased pilose antler production and growth performance in hybrid deer. However, the role of the gut microbiome in hybrid deer remains largely unknown. In this study, alpha and beta diversity analysis showed that hybridization altered the composition and structure of the gut microbiome of the offspring, with the composition and structure of the hybrid offspring being more similar to those of the paternal parents. Interestingly, the LefSe differential analysis showed that there were some significantly enriched gut microbiome in the paternal parents (such as g_Prevotellaceae UCG-003, f_Bacteroidales RF16 group; Ambiguous_taxa, etc.) and the maternal parents (including g_Alistipes, g_Anaerosporobacter, etc.), which remained significantly enriched in the hybrid offspring. Additionally, the hybrid offspring exhibited a significant advantage over the parental strains, particularly in taxa that can produce short-chain fatty acids, such as g_Prevotellaceae UCG-003, g_Roseburia, g_Succinivibrio, and g_Lachnospiraceae UCG-006. Similar to bacterial transmission, metagenomic analysis showed that some signaling pathways related to pilose antler growth ("Wnt signaling pathway," "PI3K Akt signaling pathway," "MAPK signaling pathway") were also enriched in hybrid red deer after hybridization. Furthermore, metabolomic analysis revealed that compared with the paternal and maternal parents, the hybrid offspring exhibited significant enrichment in metabolites related to "Steroid hormone biosynthesis," "Tryptophan metabolism," "Valine, leucine and isoleucine metabolism," and "Vitamin B metabolism." Notably, the metagenomic analysis also showed that these metabolic pathways were significantly enriched in hybrid deer. Finally, a correlation analysis between the gut microbiome and metabolites revealed a significant positive correlation between the enriched taxa in hybrid deer, including the Bacteroidales RF16 group, Prevotellaceae, and Succinivibrio, and metabolites, such as 7α-hydroxytestosterone, L-kynurenine, indole, L-isoleucine, and riboflavin. The study contributes valuable data toward understanding the role of the gut microbiome from red deer in hybridization and provides reference data for further screening potential probiotics and performing microbial-assisted breeding that promotes the growth of red deer pilose antlers and bodies, development, and immunity.

Identification of Cervi Cornu (Cervus elaphus) and its formula granules based on PCR-RFLP

Cervi Cornu is the ossified antler, or the base antler that falls off in the spring of the following year after the pilose antler is sawn off from Cervus elaphus or C. nippon, as a precious traditional Chinese medicine, has been recognized for its medicinal value and widely used in clinical practice. However, the origins of Cervi Cornu are miscellaneous, and Cervi Cornu is even mixed with adulterants in the market. Currently, there is a shortage of ways to identify Cervi Cornu and no standard to control the quality of Cervi Cornu. So it is valuable to develop a way to effectively identify Cervi Cornu from the adulterants. In this study, the differences in the mitochondrial barcode cytochrome b(Cytb) gene sequences of C. elaphus, C. nippon and their related species were compared and the specific single nucleotide polymorphism(SNP) sites on the Cytb sequences of Cervi Cornu were screened out. According to the screened SNPs, Cervi Cornu-specific primers dishmy-F and dishmy-R were designed. The PCR system was established and optimized, and the tolerance and feasibility of Taq polymerases and PCR systems affecting the repeatability of the PCR method were investigated. The amplification products of C. elaphus and C. nippon were digested using the restriction enzyme MseⅠ. The results showed that after electrophoresis of the product from PCR with the annealing temperature of 56 ℃ and 35 cycles, a single specific band at about 100 bp was observed for C. elaphus samples, and the product of C. elaphus samples was 60 bp shorter than that of C. nippon samples. There was no band for adulterants from other similar species such as Alces alces, Rangifer tarandus, Odocoileus virginianus, O. hemionus, Cap-reolus pygargus, Przewalskium albirostis and negative controls. The polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) method established in this study can quickly and accurately identify Cervi Cornu originated from C. elaphus in crude drugs, standard decoctions, and formula granules, and distinguish the origins of Cervi Cornu products, i.e., C. nippon and similar species. This study can be a reference for other studies on the quality standard of other formula granules of traditional Chinese medicines.

A polypeptide derived from pilose antler ameliorates CUMS-induced depression-like behavior by SENP2-PLCβ4 signaling axis

Neurogenesis is known to be closely associated with depression. We aimed to investigate whether a polypeptide monomer derived from pilose antler (polypeptide sequence LSALEGVFYP, PAP) exerts an antidepressant effect by influencing neurogenesis, and to elucidate the mechanism of its antidepressant action. Behavioral tests were performed to observe the antidepressant effect of PAP. Neurogenesis in the dentate gyrus (DG) region of hippocampus was observed by immunofluorescence. The expression of key proteins of Sentrin/SUMO-specific proteases 2 (SENP2)- Phosphoinositide-specific phospholipase C beta 4 (PLCβ4) pathway was accessed by co-immunoprecipitation (Co-IP), and the calcium homeostasis associated proteins were observed via Western blot (WB). Subsequently, temozolomide (TMZ) pharmacologically blocked neurogenesis to verify the antidepressant effect of PAP on neurogenesis. The mechanism of PAP antidepressant effect was verified by constructing a sh-SENP2 virus vector to silence SENP2 protein. Finally, corticosterone (CORT)-induced PC12 cell model was used to verify whether PAP was involved in the process of deconjugated PLCβ4 SUMOylated. The results showed that PAP improved depression-like behavior and neurogenesis induced by chronic unpredictable mild stimulation (CUMS). In addition, PAP acted on SENP2-PLCβ4 pathway to deconjugate the SUMOylation of PLCβ4 and affect calcium homeostasis. Pharmacological blockade of neurogenesis by TMZ treatment impaired the antidepressant efficacy of PAP. Knockout of SENP2 in the CUMS model attenuated the antidepressant response of PAP, and the impaired neurogenesis was not ameliorated by PAP treatment. In summary, PAP acted on the SENP2-PLCβ4 signaling pathway to inhibit the SUMOylation of PLCβ4 and maintain calcium homeostasis, thereby protecting neurogenesis and playing an antidepressant role.

Effect of pilose antler polypeptide on the mechanism of bone homeostasis in osteoporosis.

Osteoporosis stands out as a prevalent metabolic disorder, bearing significant repercussions on human well-being and overall quality of life. It remains an urgent concern within the global public health framework due to its widespread occurrence. Osteoporosis arises from an abnormal metabolism in osteoblasts and osteoclasts, resulting in a disruption of the delicate equilibrium between bone formation and bone resorption. Within this context, deer antler peptides emerge as natural active compounds, wielding a pivotal role in governing the differentiation, proliferation, and mineralization of osteoblasts, as well as influencing the activity of osteoclasts. This article aims to consolidate our comprehension of the mechanisms underpinning the dynamic balance between bone formation and resorption, meticulously orchestrated by osteoblasts and osteoclasts in osteoporosis. Furthermore, it offers a comprehensive overview of how deer antler peptides, through their modulation of relevant signaling pathways, contribute to the enhancement of bone homeostasis. These insights deepen our understanding of the pathological processes through which deer antler peptides ameliorate bone homeostasis, while also presenting novel strategies for osteoporosis management.

Retracted: Mechanism of Pilose Antler in Treatment of Osteoporosis Based on Network Pharmacology.

[This retracts the article DOI: 10.1155/2022/5298892.].

Well-known polypeptides of deer antler velvet with key actives: modern pharmacological advances.

Deer antler velvet, with kidney tonifying, promoting the production of essence and blood, strengthening tendons and bones, not only has a thousand-year medicinal history but also its modern pharmacology mainly focuses on its active polypeptides on motor, nerve, and immune systems. The purpose of this report is to fill the gap in the comprehensive, systematic, and detailed review of polypeptides during the recent 30years (1992-2023). The research method was to review 53 pharmacological articles from the Public Medicine, Web of science, ACS, and Science Direct database sources by searching the keywords "pilose antler," "deer velvet," "Pilose Antler Peptide (PAP) and Velvet Antler Polypeptide (VAP)." The results showed that deer antler polypeptides (DAPs), by regulating EGF, EGFR, MAPK, P38, ERK, NF-κB, Wnt, PI3K, Akt, MMP, AMPK, Stir1, NLRP3, HO-1, Nrf, Rho, TLR, TGF-β, Smad, Ang II, etc., revealed their effects on seven system-related diseases and their mechanisms, including osteoarthritis, intervertebral disc degeneration, osteoporosis, Alzheimer's, Parkinson's, triple-negative breast cancer, liver injury, liver fibrosis, cardiovascular disease, acute lung injury, and late-onset hypogonadism. In conclusion, DAPs have good effects on motor and other system-related diseases, but the secondary and tertiary structures of DAPs (0.5-1800 KDa) need to be further elucidated, and the structure-activity relationship study is still unavailable and needs to be covered. It is expected that this review may provide the necessary literature support for further research. The activities and mechanisms of polypeptides from the past 30years (1992-2023) are summarized covering seven systems, related diseases, and its regulatory genes and proteins.

HGF/c-Met signaling promotes the migration and proliferation of deer antler MSCs

The complete regeneration of deer antlers is based on the proliferation and differentiation of stem cells. Mesenchymal stem cells (MSCs) of antlers have an important role in antler regeneration and rapid growth and development. HGF is mainly synthesized and secreted by mesenchymal cells. After binding to its receptor c-Met, which transduces signals into cells to stimulate cell proliferation and migration in various organs to promote tissue morphogenesis and angiogenesis. However, the role and mechanism of the HGF/c-Met signaling pathway on antler MSCs are still unclear. In this study, we established antler MSCs with overexpression and interference of HGF gene by lentivirus and small interference RNA, observed the effect of HGF/c-Met signal pathway on the proliferation and migration of antler MSCs, and detected the expression of downstream related signal pathway genes, to explore the mechanism of HGF/c-MET signal pathway on the proliferation and migration of antler MSCs. The results showed that the HGF/c-Met signal affects the expression of RAS, ERK and MEK genes, regulates the proliferation of pilose antler MSCs through Ras/Raf, MEK/ERK pathway, affects the expression of Gab1, Grb2, AKT and PI3K genes, and regulates the migration of MSCs of pilose antler through Gab1/Grb2 and PI3K/AKT pathway.

Pilose antler extract restores type I and III collagen to accelerate wound healing

Granulation tissue has supporting and filling functions in wound healing. The collagen produced by fibroblast acts as a cell scaffold in the granulation tissue to facilitate the formation of new blood vessels and epithelial coverage. Previously, we extracted protein components from the pilose antler that was involved in the biological process of collagen fibril organization. They were also found to contain abundant extracellular matrix(ECM) components. Therefore, in this experiment, we used a rat model of full-thickness skin excision and fibroblasts to perform an experiment for determination of the effects of pilose antler protein extract (PAE) on collagen content and fiber synthesis during wound healing. Additionally, we further analyzed its pharmacological effects on wound healing and the possible regulatory mechanisms. We found that PAE accelerated synthesis of type I and III collagen, promoted the formation of type III collagen fibers, and reduced collagen degradation by recruiting fibroblasts. Furthermore, the extract upregulated the expression of TGF β R1 and Smad2, and initiated the entry of Smad2/Smad3 into the nucleus. After adding SB431542 to inhibit TGF-β type I receptor activity, PAE's ability to promote Smad2/Smad3 nuclear localization was weakened. These data indicate that local PAE therapy can promote the proliferation of fibroblasts, dynamically regulate the expression of TGF-β, and increase the amount of collagen and the synthesis of type III collagen fibers by promoting smad2 activity in the proliferation period, thus accelerating the regenerative healing of wounds.

Lyophilized powder of velvet antler blood improves osteoporosis in OVX-induced mouse model and regulates proliferation and differentiation of primary osteoblasts via Wnt/β-catenin pathway

The lyophilized powder of velvet antler blood (VAB) is a by-product of pilose antler, a supplement rich in amino acids, fatty acids, trace elements and vitamins, and it is expected to have anti-osteoporosis effects. The aim of our study was to provide a comprehensive assessment of the anti-osteoporosis effects of VAB in vivo and in vitro. In vivo results indicated that VAB had the protective effects on bone tissue microarchitecture degeneration and bone mass loss in ovariectomized mice. Through an in vitro study, the ability of VAB to promote proliferation, migration and differentiation of primary osteoblasts was confirmed. Further studies have shown that VAB influences cell cycle by regulating Wnt/β-catenin signaling pathway, thus promoting proliferation and differentiation of primary osteoblasts and preventing osteoporosis. According to our research results, VAB is considered to be a potential anti-osteoporosis nutrient, which may help to improve the quality of life of patients with osteoporosis.

Pilose antler (Cervus elaphus Linnaeus) polysaccharide and polypeptide extract inhibits bone resorption in high turnover type osteoporosis by stimulating the MAKP and MMP-9 signaling pathways

Ethnopharmacological relevancePilose antler is a traditional Chinese medicine used to improve kidney function, strengthen tendons and bones, and prolong life, among other uses. It is widely employed in the treatment of osteoporosis. However, the molecular mechanisms underlying the treatment of high turnover osteoporosis are not fully understood. Aim of the studyThe present study aimed to investigate the molecular mechanism underlying pilose antler polysaccharide and polypeptide extracts in inhibiting bone resorption in high turnover osteoporosis, and compare the effects of the two components alone and in combination to explore whether they could produce synergistic enhancement effects. Materials and methodsThe quantitative and qualitative characteristics of pilose antler polysaccharide and polypeptide extracts were detected by UV–visible spectrophotometry and high-performance liquid chromatography. A rat model of retinoic acid-induced osteoporosis was used to evaluate the inhibitory effect of the extracts on bone resorption. Enzyme-linked immunosorbent assay (ELISA) was used to detect the activity of factors related to high turnover type osteoporosis in rat serum. Western blotting was used to detect the expression of proteins related to the MAKP and MMP-9 signaling pathways in rat femurs. Fluorescence quantitative PCR was used to detect the transcription levels of genes related to the MAKP and MMP-9 signaling pathways in rat femur tissues. Hematoxylin and eosin staining were used to observe the osteoprotective effects of pilose antler polysaccharides and polypeptides. ResultsThe yield of pilose antler polysaccharides was 8.3%, and was mainly composed of mannose, glucosamine hydrochloride, glucuronic acid, Galacturonic acid, Galactose hydrochloride, glucose, and galactose. The yield of the polypeptides was 26.2%, and eighty percent of the molecular weight of the antler polypeptides was 1.6 kDa-7kD, among which, the molecular weight of 7kD peptide accounted for 52% of the total. Both polysaccharides and peptides could reduce the activities of TRACP, OCN, ERK1, JNK, and MMP-9 in rat serum and reduce both the protein expression and gene transcription levels of ERK1, JNK, and MMP-9 in rat femur tissue with significant differences compared with the model group. Both extracts exerted significant protective effects on rat femur tissue. The effect of pilose antler polypeptides alone was better than that of polysaccharides either alone or in combination. ConclusionsPilose antler polysaccharides, polypeptides, and their mixtures could inhibit the occurrence of bone resorption of high turnover osteoporosis by stimulating the MAKP and MMP-9 signaling pathways to reduce the expression of the ERK1, JNK, and MMP-9 genes and proteins, and could help alleviate bone loss caused by retinoic acid. Pilose antler polypeptides had a stronger effect on inhibiting bone resorption. The combination of the two components did not show synergistic enhancement effect, and the polysaccharide tended to moderate the inhibitory enhancement effect of the polypeptide.

Pilose antler polypeptides enhance chemotherapy effects in triple-negative breast cancer by activating the adaptive immune system

Water-soluble polypeptides from pilose antler (PAWPs) are a traditional Chinese functional food and have been reported to inhibit triple-negative breast cancer (TNBC) in mice. Thus, in this study, we characterized PAWPs through peptidomics, and 405 total polypeptides were finally identified. Subsequently, our results indicate that PAWPs combined with neoadjuvant chemotherapy (NAC) result in a markedly lower spleen index compared with that in other groups. Next, 25 subpopulations of T cells were identified by multi-parametric flow cytometry in the lungs, spleen, and peripheral blood of different groups. These results indicated that PAWPs combined with NAC promote the proliferation of CD3+ T cells in the spleen and significantly affect the fate of the T-cell subpopulation. Moreover, PAWPs combined with NAC increased the infiltration of CD4+ interferon-γ+ T cells into tumor tissues. Our results showed that PAWPs have immunoregulatory functions and chemosensitizing effects, with good prospects for future clinical application.

Transcriptional sequencing analysis reveals the potential use of deer antler for “tonifying the kidney and strengthening bone”

BackgroundIt is recorded in the Chinese Pharmacopoeia that deer antlers can be used to tonify the kidney and strengthen bone. Although numerous studies have demonstrated that deer antler has protective effects on the kidney and bone, its molecular mechanisms remain to be elucidated. The aim of this study was to explore the molecular mechanism underlying its effects on the bone and kidney.MethodsWater extract of pilose antler was prepared and then filtered through a 0.45 μm Hollow Fiber Cartridge (GE Healthcare, USA). The filtrate was freeze-dried by a Heto PowerDry LL3000 Freeze Dryer (Thermo, USA) and stored at − 80 °C. Rats were treated with deer antler extract (DAE) prepared in advance, and gene regulatory network in the kidney and bone was detected by RNA-Seq technique. Micro-CT was used to detect bone trabecular formation, bone mineral density (BMD) and bone volume fraction (BV/TV).ResultsThe results demonstrate that DAE could jointly heighten renal function by maintaining renal homeostasis, combating renal fibrosis, and reducing renal inflammation by regulating ion transport. Furthermore, DAE can strengthen the bone system by stimulating osteoblast differentiation and regulating bone regeneration and the bone marrow microenvironment. Micro-CT results confirmed that DAE can promote bone trabecular formation and increase BMD and BV/TV. We also identified many genes that can regulate both the kidney and bone simultaneously, which explained the theory of “kidney governing bone” at the molecular level and provided possible strategies for further application of this theory to treat diseases.ConclusionsDAE enhances renal function, maintains renal homeostasis, positively regulates skeletal system development, and increases bone mineral density. The underlying mechanism involves improving the expression levels of functional genes involved in renal function and regulation and repair, as well as genes that positively regulate skeletal system development.

Mechanism of Pilose Antler in Treatment of Osteoporosis Based on Network Pharmacology.

Background The purpose of this study was to demonstrate the pharmacodynamic material basis and molecular mechanism of pilose antler (PA) in the prevention and treatment of osteoporosis (OP) by the method of network pharmacology. Methods First, the active components of PA were screened by BATMAN-TCM database, and the component targets were obtained from the SwissTargetPrediction online tool. Moreover, the relevant target genes of OP were obtained by searching the DisGeNET database. Second, the Venn diagram was drawn to obtain the PA-OP common targets, and the protein-protein interaction (PPI) network and drug-component-target (D-C-T) network were constructed by Cytoscape software. Finally, the GO functional annotation and KEGG pathway enrichment analysis of common targets were performed using the Metascape online tool. Results 82 common targets were identified by generating a Venn diagram. The PPI network of 82 common targets indicated that the top 5 nodal targets, including PIK3CA, MAPK1, ESR1, AKT1, and SRC, were strongly associated with other proteins. The D-C-T network suggested that the active components with high degree of connectivity include Prostaglandin E1, 17-Beta-Estradiol, Alpha-Estradiol, and Estrone. Furthermore, the GO enrichment analysis revealed that the biological process categories were dominated by response to peptide, cellular response to lipid, regulation of MAPK cascade, and so on. Additionally, the KEGG pathway analysis indicated the estrogen signaling pathway, osteoclast differentiation, and HIF-1 signaling pathway might have critical effects on the development of OP. Conclusion The study shows that PA has the characteristics of multi-component, multi-target, and multi-pathway in treating osteoporosis.

The Protective Effect of Pilose Antler Peptide on CUMS-Induced Depression Through AMPK/Sirt1/NF-κB/NLRP3-Mediated Pyroptosis.

Background: Pilose antler peptide (PAP), prepared from the pilose antler of Cervus nippon Temminck, is widely used in traditional Chinese medicine (TCM) against various inflammatory disorders. TCM prescriptions containing pilose antler are often prescribed clinically to treat depression. However, the pharmacological mechanisms of how PAP, against inflammation, prevents and treats depression remain poorly understood. Methods: PAP was identified by de novo sequencing and database searching. Then, behavioral tests were conducted to investigate the effect of PAP on CUMS-exposed mice. In parallel, Nissl staining and Golgi-Cox staining were used for exploring the effect of PAP on neural cells and dendritic spine density. Additionally, the expression of key proteins of the AMPK/Sirt1/NF-κB/NLRP3 pathway was analyzed by Western blot. Finally, the CUMS procedure was conducted for 6 weeks. At the 5th week, PAP and fluoxetine (Flu) were intragastrically treated for 2 weeks. The silencing information regulator-related enzyme 1 (Sirt1) inhibitor EX-527 and the AMP-activated protein kinase (AMPK) inhibitor dorsomorphin were employed to investigate the effects of Sirt1 and AMPK on PAP-mediated depression. Results: PAP attenuated the behavior alteration caused by CUMS stimulation, decreased the number of neurons, and restored the dendritic spine density. PAP treatment effectively upregulated the expressions of p-AMPK and Sirt1 and suppressed the expressions of Ac-NF-κB, NLRP3, Ac-Caspase-1, GSDMD-N, Cleaved-IL-1β, and Cleaved-IL-18. Moreover, selectively inhibited Sirt1 and AMPK were able to compromise the therapeutic effect of PAP on depression. Conclusion: The present work indicated that PAP has a protective effect on CUMS-induced depression. In addition, AMPK and Sirt1 played critical roles in the PAP-relieved depression. PAP might be a potential therapeutic option for treating depression.

Pilose antler polypeptides promote chemosensitization and T-cell infiltration of triple-negative breast cancer

• Water-soluble polypeptides from pilose antler (PAWPs) enhance chemosensitization. • The PAWPs reduce the side effects of neoadjuvant chemotherapy (NAC). • NAC + PAWPs promotes T cell infiltration and improves T cell populations. • NAC + PAWPs via TGF-β1-SMAD3 signaling pathway to reduce CAFs infiltration. In this study, we aimed to determine the effects of combined neoadjuvant chemotherapy (NAC) and water-soluble polypeptides from pilose antler (PAWP) administration on mouse TNBC 4T1 tumors using multiplex immunohistochemistry and flow cytometry to enhance chemosensitization and alleviate immunosuppression. Our findings reveal that PAWPs significantly reduce tumor growth and decrease weight loss in combination with NAC treatment. Additionally, PAWP treatment promoted both an increase in immune-cell levels in peripheral blood and CD4 + and CD8 + T-cell infiltration into the tumor. Furthermore, we observed reduced expression of transforming growth factor-β1, actin α2, and vimentin under combined PAWP + NAC treatment. These findings demonstrate the efficacy of PAWPs as a functional food capable of regulating the immune system and inhibiting tumor progression as well as their efficacy as a potential adjuvant supplement to NAC for TNBC treatment.

Pilose Antler Peptide-3.2KD Ameliorates Adriamycin-Induced Myocardial Injury Through TGF-β/SMAD Signaling Pathway.

Adriamycin (ADR)-based combination chemotherapy is the standard treatment for some patients with tumors in clinical, however, long-term application can cause dose-dependent cardiotoxicity. Pilose Antler, as a traditional Chinese medicine, first appeared in the Han Dynasty and has been used to treat heart disease for nearly a thousand years. Previous data revealed pilose antler polypeptide (PAP, 3.2KD) was one of its main active components with multiple biological activities for cardiomyopathy. PAP-3.2KD exerts protective effects againt myocardial fibrosis. The present study demonstrated the protective mechanism of PAP-3.2KD against Adriamycin (ADR)-induced myocardial injury through using animal model with ADR-induced myocardial injury. PAP-3.2KD markedly improved the weight increase and decreased the HW/BW index, heart rate, and ST height in ADR-induced groups. Additionally, PAP-3.2KD reversed histopathological changes (such as disordered muscle bundles, myocardial fibrosis and diffuse myocardial cellular edema) and scores of the heart tissue, ameliorated the myocardial fibrosis and collagen volume fraction through pathological examination, significantly increased the protein level of Bcl-2, and decreased the expression levels of Bax and caspase-3 in myocardial tissue by ELISA, compared to those in ADR-induced group. Furthermore, ADR stimulation induced the increased protein levels of TGF-β1 and SMAD2/3/4, the increased phosphorylation levels of SMAD2/3 and the reduced protein levels of SMAD7. The expression levels of protein above in ADR-induced group were remarkably reversed in PAP-3.2KD-treated groups. PAP-3.2KD ameliorated ADR-induced myocardial injury by regulating the TGF-β/SMAD signaling pathway. Thus, these results provide a strong rationale for the protective effects of PAP against ADR-induced myocardial injury, when ADR is used to treat cancer.

Enhanced In Vitro and In Vivo Efficacy of Alginate/Silk Protein/Hyaluronic Acid with Polypeptide Microsphere Delivery for Tissue Regeneration of Articular Cartilage

Alginate/Silk fibroin/hyaluronic acid (ALG/SF/HA) nanocomposites were synthesised using blending, inter-linking, and lyophilization methods. We investigated the physicochemical properties of the resulting nanocomposites, including their water retention, weight loss, porosity and cytocompatibility. The optimum ratios of the ALG/SF/HA scaffolding were 3:6.5:0.5. Nanocomposites with optimum ratios were then prepared by integrating pilose antler polypeptides (PAPS) to poly(lactic-co-glycolic acid) (PLGA) microspheres, and the performance was investigated. PAPS-ALG/SF/HA nanocomposites exhibited desirable adhesions and proliferations. Rabbit cartilage deficiencies was developed by the animal model. The cartilage repair effects deficiencies were detected and analyzed between PAPS-SF/ALG/ALG/SF/HA, and control activity classes. The deficiencies were virtually fully remedied after 13 weeks in the presence of PAPS-ALG/SF/HA class, suggesting that the PAPS-ALG/SF/HA nanocomposites had a positive effects on joint cartilage repair.

Peptidomic analysis of pilose antler and its inhibitory effect on triple-negative breast cancer at multiple sites.

Pilose antler (PA) is a traditional Chinese functional food that has been reported to inhibit breast cancer; however, the specific substances that exert this effect and the underlying mechanisms remain unknown. This study aims to identify the specific proteins in PA water-soluble polypeptides (PAWPs) that are involved in cancer inhibition and determine the effects of PAWPs on triple-negative breast cancer in mice. In this study, peptidomic analysis of 105 varieties of polypeptides from PAWPs was carried out using LC-MS, 22 of which had functions that could potentially suppress tumors, including endopeptidase inhibitors, metal ion-binding proteins, angiogenesis inhibitors, intercellular adhesion proteins, and extracellular matrix repair proteins. Furthermore, we showed that intragastric administration of PAWPs into mice inhibited the growth and metastasis of triple-negative 4T1 breast tumors. PAWPs activated the expression of cleaved-caspase3 and increased tumor apoptosis, resulting in the reduction of platelet-endothelial cell adhesion molecule (PECAM-1/CD31) expression and the number of blood vessels, as well as the inhibition of matrix metalloproteinase (MMP) 2 and 9, increasing the ratio of Cadherin-1 (CDH1)/Cadherin-2 (CDH2) and inhibiting epithelial-mesenchymal transition (EMT) in these tumors. Therefore, PAWPs inhibit the progression and metastasis of triple-negative 4T1 breast cancer at multiple key sites in mice and contain various tumor suppressor proteins that are potentially involved in these processes.