Drug conjugates for the treatment of lung cancer: from drug discovery to clinical practice.

A drug conjugate consists of a cytotoxic drug bound via a linker to a targeted ligand, allowing the targeted delivery of the drug to one or more tumor sites. This approach simultaneously reduces drug toxicity and increases efficacy, with a powerful combination of efficient killing and precise targeting. Antibody‒drug conjugates (ADCs) are the best-known type of drug conjugate, combining the specificity of antibodies with the cytotoxicity of chemotherapeutic drugs to reduce adverse reactions by preferentially targeting the payload to the tumor. The structure of ADCs has also provided inspiration for the development of additional drug conjugates. In recent years, drug conjugates such as ADCs, peptide‒drug conjugates (PDCs) and radionuclide drug conjugates (RDCs) have been approved by the Food and Drug Administration (FDA). The scope and application of drug conjugates have been expanding, including combination therapy and precise drug delivery, and a variety of new conjugation technology concepts have emerged. Additionally, new conjugation technology-based drugs have been developed in industry. In addition to chemotherapy, targeted therapy and immunotherapy, drug conjugate therapy has undergone continuous development and made significant progress in treating lung cancer in recent years, offering a promising strategy for the treatment of this disease. In this review, we discuss recent advances in the use of drug conjugates for lung cancer treatment, including structure-based drug design, mechanisms of action, clinical trials, and side effects. Furthermore, challenges, potential approaches and future prospects are presented.

Sheng Mai Yin shows anti-fatigue, anti-hypoxia and cardioprotective potential in an experimental joint model of fatigue and acute myocardial infarction.

ETHNOPHARMACOLOGICAL RELEVANCE: Cardiovascular disease (CVD) and fatigue are two common diseases endangering human life and health that may interact and reinforce one another. Myocardial infarction survivors frequently experience fatigue, and acute myocardial infarction (AMI) is one of the most common cardiovascular diseases that cause fatigue-induced sudden death. Sheng Mai Yin (SMY), a Chinese medicine prescription, is traditionally used for the treatment of diabetes and cardiovascular disease, and has been demonstrated to reduce fatigue and safeguard cardiac function. AIM OF THE STUDY: This study aims to investigate the effects and underlying mechanisms of SMY in treating fatigue and AMI. MATERIALS AND METHODS: The pharmacological mechanisms of SMY in treating fatigue and AMI were predicted by bioinformatics and network pharmacology methods. After administering SMY at high, medium and low doses, the swimming time to exhaustion, hemoglobin level, serological parameters and hypoxia tolerance time were detected in C57BL/6N mice, and the left ventricular ejection fractions (LVEF), left ventricular fractional shortening (LVFS), grasp strength, cardiac histopathology, serological parameters and the expression of PINK1 and Parkin proteins were examined in Wistar rats. RESULTS: 371 core targets for SMY and 282 disease targets for fatigue and AMI were obtained using bioinformatics and network pharmacology methods. Enrichment analysis of target genes revealed that SMY might interfere with fatigue and AMI through biological processes such as mitochondrial autophagy, apoptosis, and oxidative stress. For in vivo experiments, SMY showed significant anti-fatigue and hypoxia tolerance effects in mice; It also improved the cardiac function and grasp strength, decreased their cardiac index, myocardial injury and fibrosis degree, and induced serological parameters levels and the expression of PTEN-induced putative kinase 1 (PINK1) and Parkin proteins in myocardium, suggesting that SMY may exert cardioprotective effects in a joint rat model of fatigue and AMI by inhibiting excessive mitochondrial autophagy. CONCLUSION: This study revealed the anti-fatigue, anti-hypoxia and cardioprotective effects of SMY in a joint model of fatigue-AMI, and the pharmacological mechanism may be related to the inhibition of mitochondrial autophagy in cardiomyocytes through the PINK1/Parkin pathway. The discoveries may provide new ideas for the mechanism study of traditional Chinese medicine, especially complex prescriptions, in treating fatigue and AMI.

Acute, subchronic toxicity and genotoxicity studies of JointAlive, a traditional Chinese medicine formulation for knee osteoarthritis.

AIM: In vivo and in vitro toxicity tests of JointAlive® were studied in animal models to support the safe use of JointAlive® as a drug for knee osteoarthritis treatment. METHODS: The acute toxicity study in Sprague Dawley (SD) rats was conducted at a 20 g/kg bw/day dose of JointAlive®. For 13-week subchronic toxicity tests, SD rats were orally dosed daily with 0.5, 1.5 and 5 g/kg bw/day of JointAlive®. To assess the potential genotoxicity, Ames test, cellular chromosome aberration and mouse micronucleus test in vivo were carried out. RESULTS: Based on a lack of notable findings other than histopathology finding of co-incidental prostate inflammation at the high dose, the "No Observed Adverse Effect Level (NOAEL)" of JointAlive® was concluded as 5 g/kg bw/day in males and females. Results also indicated that JointAlive® has no risk of genotoxicity. CONCLUSIONS: General toxicity and genotoxicity studies empirically demonstrated that JointAlive® poses a low risk of potential health risks, providing safety supports for the application of JointAlive® as a potential drug candidate to treat knee osteoarthritis.

Application of Adjustable Skin Stretchers in Repairing Wound-Related Defects.

Objective: To explore the application value of adjustable skin stretchers for repairing skin wound defects. Methods: Twenty patients with skin defects were included in this study. The largest defect was measured to be 45.4 cm × 13.3 cm (length × width) and the smallest one was 4.4 cm × 3.2 cm (length × width). All patients were subjected to adjustable skin stretchers and the short- and long-term clinical efficacy was evaluated. Results: The wounds of all enrolled patients were healed completely except for one patient with a dorsal foot infection (the patient requested to return to the local county hospital for further treatment), with a total satisfaction of 100%. Postoperative 3-month follow-up showed scar formation, a little local hyperpigmentation, normal skin elasticity, and intact organs of involved cases, thus signifying the significant impact of adjacent joint activities. Conclusion: Adjustable skin stretchers can accurately control the tension on wound margins, breaking the limitation of previous stretchers to provide objective quantitative indicators for clinical application. These stretchers are characterized by high use-value and are worth promoting.

Quantitative proteomics reveals the therapeutic effects of RFAP against depression via pathway regulation of long-term depression and potentiation.

Ethnopharmacological relevance: RFAP is a compound extraction complex of four Traditional Chinese Medicine (TCM), including the dry bark of Paeonia lactiflora Pall. (Radix Paeoniae Alba), Gardenia jasminoides J. Ellis (Fructus Gardeniae), Albizia julibrissin Durazz. (Albizia julibrissin Durazz), and Paeonia × suffruticosa Andrews (Peony bark). Not only RFAP but also the individual ingredients have been commonly used for the treatment of depression in the clinic. However, the underlying mechanism of pharmacology is difficult to interpret since its holistic and multidrug nature. Aim of the study: This study aimed to elucidate the potential antidepressant mechanism of RFAP in the treatment of chronic unpredictable mild stress (CUMS) rats' model via the quantitative proteomics approach. Materials and methods: We established the CUMS rats' model and evaluated the efficacy of RFAP using multiple behavior assays, including the sugar preference test, open field test, and forced swimming test. Then label-free quantitative proteomics analyses were performed to evaluate the integrated changes of proteome profiling in control, CUMS, RFAP low dose, and RFAP high dose groups. Finally, we validated the critical changed proteins in the pathways of long-term depression and potentiation via RT-PCR and Western blotting assays. Results: We successfully established the CUMS rats' model. The behavior assays indicated that the rats demonstrated a tendency to behavioral despair after four weeks. Label-free quantitative proteomics showed that 107 proteins were significantly upregulated and 163 proteins were downregulated in the CUMS group compared to the control group. These differentially expressed proteins were involved in long-term potentiation, long-term depression, nervous system development, neuronal synaptic structural constituent of ribosome, ATP metabolic process, learning or memory, and cellular lipid metabolic process. RFAP treatment partially restored the differentially expressed protein profile. The protective effect of RFAP on behavioral assessment were consistent with the results of proteomics. Conclusions: The results indicated that RFAP exerted a synergistic effect on CUMS by regulating long-term inhibition and potentiation-related proteins.

Design, synthesis and biological evaluation of novel 9-N-substituted-13-alkylberberine derivatives from Chinese medicine as anti-hepatocellular carcinoma agents.

A series of novel 9-N-substituted-13-alkylberberine derivatives from Chinese medicine were designed and synthesized with improved anti-hepatocellular carcinoma (HCC) activities. The optimal compound 4d showed strong activities against HepG2, Sk-Hep-1, Huh-7 and Hep3B cells with IC50 values of 0.58-1.15 µM, which were superior to positive reference cisplatin. Interestingly, 4d exhibited over 40-fold more potent activity against cisplatin-resistant HepG2/DPP cells while showing lower cytotoxicity in normal LX-2 cells. The mechanism studies revealed 4d greatly stabilized G-quadruplex DNA leading to intracellular c-MYC expression downregulation, blocked G2/M-phase cell cycle by affecting related p-cdc25c, cdc2 and cyclin B1 expressions, and induced apoptosis by a ROS-promoted PI3K/Akt-mitochondrial pathway. Furthermore, 4d possessed good pharmacokinetic properties and significantly inhibited the tumor growth in the H22 liver cancer xenograft mouse model without obvious toxicity. Altogether, the remarkably biological profiles of 4d both in vitro and in vivo would make it a promising candidate for HCC therapy.

A novel solvent-free co-grinding preparation improves curcumin bioavailability in healthy volunteers: A single-center crossover study.

Curcumin, from the rhizome of turmeric (Curcuma longa L.), has a wide variety of biological activities. Unfortunately, its poor water-solubility greatly limits its bioavailability. The purpose of this study was to evaluate CUMINUP60®, a novel preparation utilizing a solvent-free, co-grinding method designed to improve curcumin's bioavailability. We performed a single-center crossover experiment to compare the new product with standard 95% curcumin in the blood plasma of twelve healthy adults (10 males, 2 females). Total bioavailability of curcumin and its sulfate and glucuronide conjugates from the test product, measured by their areas under the curve over 12 h (AUC0-T), showed a combined increase of 178-fold over standard curcumin and its conjugates from the reference product. The new product represents a significant improvement for providing greater bioavailability of curcumin, as compared with several other branded preparations. It therefore has broad applications for preparing curcumin as a more effective health ingredient in functional foods, beverages, and nutraceuticals.

Safety evaluation of CuminUP60® - A novel curcumin complex.

Curcuma longa L. is one of the most recognized Curcuma species (Sharifi-Rad et al., 2020 [3]). Curcumin, the primary polyphenolic compound found in turmeric has been used for a variety of purposes for centuries. CuminUP60® is a curcumin complex composed of Curcuma longa L. rhizome extract and Poloxamer 407. The results of GLP compliant in vitro and in vivo safety studies conducted with CuminUP60® including a bacterial reverse mutation assay, an in vitro mammalian cell chromosome aberration study and an in vivo micronucleus study are reported here. In addition, a GLP compliant, a single dose toxicity study in Sprague-Dawley rats and a 4-week repeat dose study were also conducted. CuminUP60® was shown to not be mutagenic in a number of in vitro and one in vivo study, the results of which are reported here. A single oral dose of 5000 mg CuminUP60® was well tolerated by male and female Sprague-Dawley rats. The no observed adverse effect level (NOAEL) for CuminUP60® in male and female Sprague-Dawley rats in a 4-week repeat dose study was determined to be 1000 mg/kg bw/day.

The Ameliorative Effect and Mechanisms of Ruditapes philippinarum Bioactive Peptides on Obesity and Hyperlipidemia Induced by a High-Fat Diet in Mice.

In this study, bioactive peptides (RBPs) from Ruditapes philippinarum were prepared by fermentation with Bacillus natto and the effect and mechanisms of RBPs on obesity and hyperlipidemia were explored in mice. We found that RBPs significantly reduced body weight, adipose tissue weight, accumulation of hepatic lipids, and serum levels of total cholesterol (CHO), triglyceride (TG), and low-density lipoprotein (LDL). Mechanistic studies showed that RBPs up-regulated the hepatic expression of genes related to lipolysis, such as hormone-sensitive lipase (HSL), phosphorylated AMP-activated protein kinase (p-AMPK), and peroxisome proliferator-activated receptors α (PPARα), and down-regulated the expression of peroxisome proliferator-activated receptors γ (PPARγ) which is related to lipid synthesis. In addition, RBPs could attenuate obesity and hyperlipidemia by regulating disordered gut microbiota composition, such as increasing the abundance of microflora related to the synthesis of short chain fatty acids (SCFAs) (Bacteroidetes, Prevotellaceas_UCG_001, norank_f_Muribaculaceae, and Odoribacter) and controlling those related to intestinal inflammation (reduced abundance of Deferribacteres and increased abundance of Alistipes and ASF356) to exert anti-obesity and lipid-lowering activities. Our findings laid the foundation for the development and utilization of RBPs as a functional food to ameliorate obesity and hyperlipidemia.

Positive Effect of a Pea-Clam Two-Peptide Composite on Hypertension and Organ Protection in Spontaneously Hypertensive Rats.

In the present study, we prepared pea peptides with high angiotensin-converting enzyme (ACE) inhibitory activity in vitro using an enzymatic hydrolysis of pea protein and compounded them with clam peptides to obtain a pea-clam double peptide. The effects of the two-peptide composite and pea peptides on hypertension and the damage-repair of corresponding organs were studied in spontaneously hypertensive rats (SHRs). We found that both pea peptides and the two-peptide composite significantly reduced the blood pressure upon a single or long-term intragastric administration, with the two-peptide composite being more effective. Mechanistically, we found that the two-peptide composite could regulate the renal renin-angiotensin system (RAS), rebalance gut microbial dysbiosis, decrease renal and myocardial fibrosis, and improve renal and cardiac function and vascular remodeling. Additionally, hippocampal lesions caused by hypertension were also eliminated after two-peptide composite administration. Our research provides a scientific basis for the use of this two-peptide composite as a safe antihypertension ingredient in functional foods.

Investigation Driven by Network Pharmacology on Potential Components and Mechanism of DGS, a Natural Vasoprotective Combination, for the Phytotherapy of Coronary Artery Disease.

Phytotherapy offers obvious advantages in the intervention of Coronary Artery Disease (CAD), but it is difficult to clarify the working mechanisms of the medicinal materials it uses. DGS is a natural vasoprotective combination that was screened out in our previous research, yet its potential components and mechanisms are unknown. Therefore, in this study, HPLC-MS and network pharmacology were employed to identify the active components and key signaling pathways of DGS. Transgenic zebrafish and HUVECs cell assays were used to evaluate the effectiveness of DGS. A total of 37 potentially active compounds were identified that interacted with 112 potential targets of CAD. Furthermore, PI3K-Akt, MAPK, relaxin, VEGF, and other signal pathways were determined to be the most promising DGS-mediated pathways. NO kit, ELISA, and Western blot results showed that DGS significantly promoted NO and VEGFA secretion via the upregulation of VEGFR2 expression and the phosphorylation of Akt, Erk1/2, and eNOS to cause angiogenesis and vasodilation. The result of dynamics molecular docking indicated that Salvianolic acid C may be a key active component of DGS in the treatment of CAD. In conclusion, this study has shed light on the network molecular mechanism of DGS for the intervention of CAD using a network pharmacology-driven strategy for the first time to aid in the intervention of CAD.

Functional yogurt fermented by two-probiotics regulates blood lipid and weight in a high-fat diet mouse model.

We investigated the blood lipid regulation effects and mechanism of a functional Natto yogurt in a high-fat diet-induced hyperlipidemia mouse model. Natto yogurt was characteristically fermented by Bacillus natto and Lactobacillus plantarum with milk-soy dual protein as substrates. After 5 weeks of Natto yogurt consumption, the body weight, fat, and liver weight of mice were significantly improved, while serum levels of TG, TC, LDL, ALT, TBIL, and TBA were reduced. Natto yogurt significantly decreased the area of liver fat infiltration and the number of lipid droplets. In mechanism, we found that Natto yogurt can inhibit fatty acid synthesis and enhance fatty acid catabolism by regulating the expression of PPARα, PPARγ, CD36 and FAS in the liver. Moreover, Natto yogurt increased the ratio of Bacteroidetes to Firmicutes in the intestine. These results provide a possibility for Natto yogurt as a dual protein functional food to prevent and treat hyperlipidemia and obesity. PRACTICAL APPLICATIONS: Traditional-fermented yogurt promotes nutritional absorption and reduces blood pressure and fat, while Bacillus natto and its fermented food have been proved to play a significant role in improving cardiovascular and cerebrovascular diseases and obesity. Therefore, we developed a new dual protein functional yogurt (Natto yogurt) fermented by B. natto and Lactobacillus plantarum with milk and soy as substrates. We found that Natto yogurt could notably regulate blood lipid by inhibiting the synthesis of fatty acids, accelerating the catabolism of fatty acids, reducing liver damage, and increasing the abundance of beneficial intestinal microorganisms. This study suggested that Natto yogurt could improve hyperlipidemia and obesity as a safe, effective, and healthy functional food.

Chinese Herbal Extracts Exert Neuroprotective Effect in Alzheimer's Disease Mouse Through the Dopaminergic Synapse/Apoptosis Signaling Pathway.

Background: Alzheimer's disease (AD) as an age-related, irreversible neurodegenerative disease, characterized by cognitive dysfunction, has become progressively serious with a global rise in life expectancy. As the failure of drug elaboration, considerable research effort has been devoted to developing therapeutic strategies for treating AD. TCM is gaining attention as a potential treatment for AD. Gastrodia elata Blume, Polygala tenuifolia Willd., Cistanche deserticola Ma, Rehmannia lutinosa (Gaertn.)DC., Acorus gramineus Aiton, and Curcuma longa L. (GPCRAC) are all well-known Chinese herbs with neuroprotective benefits and are widely used in traditional Chinese decoction for AD therapy. However, the efficacy and further mechanisms of GPCRAC extracts in AD experimental models are still unclear. The purpose of this study was to investigate the synergistic protective efficacy of GPCRAC extracts (composed of extracts from these six Chinese medicines), and the protein targets mediated by GPCRAC extracts in treating AD. Methods: Scopolamine-induced cognitive impairment mouse model was established to determine the neuroprotective effects of GPCRAC extracts in vivo, as shown by behavioral tests and cerebral cholinergic function assays. To identify the potential molecular mechanism of GPCRAC extracts against AD, label-free quantitative proteomics coupled with tandem mass spectrometry (LC-MS/MS) were performed. The integrated bioinformatics analysis was applied to screen the core differentially expressed proteins in vital canonical pathways. Critical altered proteins were validated by qPCR and Western blotting. Results: Administration of GPCRAC extracts significantly recovered scopolamine-induced cognitive impairment, as evidenced by the improved learning and memory ability, increased Ach content and ChAT activity, as well as decreased AchE activity in the hippocampus of mice. In total, 390 proteins with fold-change>1.2 or <0.83 and p < 0.05 were identified as significant differentially expressed proteins, of which 110 were significantly up-regulated and 25 were significantly down-regulated between control and model group. By mapping the significantly regulated proteins, we identified five hub proteins: PPP2CA, Gsk3ß, PP3CC, PRKACA, and BCL-2 that were associated with dopaminergic synapse and apoptosis signaling pathway, respectively. Western blotting and QPCR demonstrate that the expression levels of these core proteins could be significantly improved by the administration of GPCRAC extracts. These pathways and some of the identified proteins are implicated in AD pathogenesis. Conclusion: Administration of GPCRAC extracts was effective on alleviating scopolamine-induced cognitive impairment, which might be through modulation of dopaminergic synapse and apoptosis signaling pathway. Consequently, our quantitative proteome data obtained from scopolamine-treated model mice successfully characterized AD-related biological alterations and proposed novel protein biomarkers for AD.

Positive effect of compound amino acid chelated calcium from the shell and skirt of scallop in an ovariectomized rat model of postmenopausal osteoporosis.

BACKGROUND: Osteoporosis has become an important public health issue with the increase of aging population, and afflicts millions of people worldwide, particularly elderly or postmenopausal women. In the present study, we prepared compound amino acid chelated calcium (CAA-Ca) from processing by-products of Chlamys farreri, and evaluated its effect on postmenopausal osteoporosis with an ovariectomized (OVX) rat model. RESULTS: A 60-day treatment of OVX rats with CAA-Ca significantly enhanced the bone mineral density (BMD) and the bone calcium content. Meanwhile, some bone morphometric parameters, trabecular bone number (Tb.N), trabecular bone volume fraction (BV/TV), trabecular bone thickness (Tb.Th) and cortical bone wall thickness (Ct.Th), were also increased by 8.20%, 118.18%, 32.99% and 19.10%, respectively. In addition, the alkaline phosphatase (ALP) levels in serum were significantly reduced after CAA-Ca treatment, while the blood calcium levels were increased. Mechanistically, CAA-Ca down-regulated the levels of receptor activator of nuclear factor-κB (RANK) and receptor activator of nuclear factor-κB ligand (RANKL), and up-regulated osteoprotegerin (OPG) levels in osteoclasts, inhibiting bone resorption and bone loss. Meanwhile, CAA-Ca treatment raised ß-catenin levels and lowered Dickkopf1 (DKK1) levels in the Wnt signaling pathway of osteoblasts, which can promote calcium absorption and bone formation. CONCLUSION: The results suggested that CAA-Ca promoted bone formation, inhibited bone resorption and improved bone microstructure. Therefore, this study contributes to the potential application of CAA-Ca as a functional food resource in the treatment of postmenopausal osteoporosis. © 2021 Society of Chemical Industry.

Quantitative proteomics reveal the protective effects of EDS against osteoarthritis via attenuating inflammation and modulating immune response.

ETHNOPHARMACOLOGICAL RELEVANCE: Epimedium brevicornu Maxim, Dioscorea nipponica Makino, and Salvia miltiorrhiza Bunge formula (EDS) are three traditional Chinese medicines commonly combined and used to treat osteoarthritis (OA). However, the mechanism of its therapeutic effect on OA is still unclear. AIM OF THE STUDY: The aim of this study was to investigate the potential anti osteoarthritis mechanism of EDS in the treatment of OA rats' model by quantitative proteomics. MATERIALS AND METHODS: A papain-induced rat OA model was established, and then EDS was intragastrically administered for 28 days. A label-free quantification proteomics was performed to evaluate the holistic efficacy of EDS against OA and identify the possible protein profiles mechanisms. The expression levels of critical changed proteins were validated by RT-qPCR and Western blotting. The effects of EDS were then assessed by evaluating pathologic changes in the affected knee joint and measuring pressure pain threshold, acoustic reflex threshold, angle of joint curvature. RESULTS: Proteomics analysis showed that 62 proteins were significantly upregulated and 208 proteins were downregulated in OA group compared to control group. The changed proteins were involved in activation of humoral immunity response, complement cascade activation, leukocyte mediated immunity, acute inflammatory response, endocytosis regulation, and proteolysis regulation. The EDS treatment partially restored the protein profile changes. The protective effects of EDS on pathologic changes in OA rats' knee joint and pain threshold assessment were consisted with the proteomics results. CONCLUSIONS: The results suggest that EDS exerted synergistic therapeutic efficacies to against OA through suppressing inflammation, modulating the immune system, relieving joint pain, and attenuating cartilage degradation.

Eucommia, Cuscuta, and Drynaria Extracts Ameliorate Glucocorticoid-Induced Osteoporosis by Inhibiting Osteoclastogenesis Through PI3K/Akt Pathway.

Osteoporosis is one of the most common diseases in the world which resulted in heavy socioeconomic burden and a public health threat. Glucocorticoid-induced osteoporosis (GIO) is the most common secondary reason of osteoporosis. Therapeutic strategies using traditional Chinese medicine are under investigation for osteoporosis, with efforts to improve efficacy and clarify the mechanism. The combination of Eucommia, Cuscuta, and Drynaria is widely used in traditional Chinese decoction for osteoporosis treatment, but the experimental efficacy and mechanism are still unclear. Administration of E.C.D. extracts (Eucommia, Cuscuta, and Drynaria) in experimental GIO rats resulted in decreased urinal calcium, phosphorus loss, and decreased expression of RANKL, CTX in serum, increased serum calcium, phosphorus, and OPG level. E.C.D. extracts also improved bone density, structural integrity, and biomechanical function in experimental GIO rats. These finding were associated with E.C.D. extracts' treatment efficacy to GIO in vivo. The balance between osteoclast and osteoblast activity is essential for bone remodeling and bone related disease. The E.C.D. extracts inhibited Raw 264.7 cell differentiation to osteoclast in vitro. On the other hand, it promoted OPG expression of bone marrow mesenchymal stromal cells (MSCs) which can suppress the osteoclast genesis. E.C.D. extracts also increased the Wnt1 and Runx2 expression which are related to osteoblast formation. It also regulated the paracrine effect of MSC to inhibit osteoclast differentiation. The analysis of HPLC and comprehensive pharmacology identified the constituents of E.C.D. extracts and the potential osteoporosis-related targets mediated by E.C.D. extracts. The KEGG enrichment analysis suggested that PI3K/Akt pathway may be involved in the regulation osteoclast genesis by E.C.D. extracts and the result of Western blot of vitro assays proved it. Collectively, these data demonstrate E.C.D. extracts can inhibit osteoclast differentiation to foster experimental osteoporosis both in vivo and in vitro and it may exert the function of inhibiting osteoclast differentiation through PI3K/Akt pathway.

Antimicrobial and Preservative Effects of the Combinations of Nisin, Tea Polyphenols, Rosemary Extract, and Chitosan on Pasteurized Chicken Sausage.

ABSTRACT: This study was conducted to evaluate the antimicrobial and preservative effects of the combinations of nisin (NS), tea polyphenols (TP), rosemary extract (RE), and chitosan (CS) on pasteurized chicken sausage. An orthogonal test revealed that the most effective preservative was a mixture of 0.05% NS plus 0.05% TP plus 0.03% RE plus 0.55% CS (weight by sausage weight). This mixture had antimicrobial and antioxidant effects in pasteurized chicken sausage and extended the shelf life to >30 days at 4°C. The inhibitory effects of NS, TP, RE, and CS were also evaluated against Pseudomonas aeruginosa, lactic acid bacteria (LAB), and Staphylococcus aureus, the dominant spoilage and pathogenic bacteria in pasteurized chicken sausage. NS had the greatest inhibitory effect on LAB and S. aureus, with inhibitory zone diameters of 19.7 and 17.8 mm, respectively. TP had the largest inhibitory effect on P. aeruginosa, with a clear zone diameter of 18.2 mm. These results indicate that the combination of NS, TP, RE, and CS could be used as a natural preservative to efficiently inhibit the growth of microorganisms in pasteurized chicken sausage and improve its safety and shelf life.

Identification and Antihypertension Study of Novel Angiotensin I-Converting Enzyme Inhibitory Peptides from the Skirt of Chlamys farreri Fermented with Bacillus natto.

The aim of this study was to isolate the angiotensin I-converting enzyme (ACE) inhibitory peptides from the skirt of Chlamys farreri fermented with Bacillus natto and to explore the antihypertension effect through in vivo studies. ACE inhibitory peptides were purified from the fermentation mixture by ultrafiltration, gel filtration chromatography, and reversed-phase high-performance liquid chromatography sequentially. The amino acids' sequence of the five novel ACE inhibitory peptides were identified by liquid chromatography-tandem mass spectrometry. Animal experiments demonstrated that the novel ACE inhibitory peptides significantly reduced the blood pressure in spontaneously hypertensive rats after a single or long-time treatment. Potential mechanisms were explored, and the results indicated that the novel peptides could regulate the renal renin-angiotensin system, improve vascular remodeling, inhibit myocardial fibrosis, and rebalance the gut microbial dysbiosis. Our results suggest that the fermentation products of the Chlamys farreri skirt by B. natto are potential sources of active peptides processing antihypertension activities.

Emulsified blend film based on konjac glucomannan/carrageenan/ camellia oil: Physical, structural, and water barrier properties.

The objective of this study was to develop a new hydrophobic film based on konjac glucomannan and kappa-carrageenan (KGM-KC) incorporating camellia oil (CO) (2, 4, and 6 %). CO was directly emulsified as a dispersed phase into KGM-KC matrix. The physical, structural, and water barrier properties of the film were studied. The results of Fourier transform infrared and scanning electron microscopy suggested that CO was successfully distributed in KGM-KC matrix by emulsification. Contact angle of the film indicated that addition of CO increased the hydrophobicity and water-resistance properties of film, which corresponding to the moisture content, total soluble mass, water vapor permeability, water vapor adsorption kinetics and water vapor adsorption isotherms. Addition of CO by emulsification improved thermal stability of film, optical properties, and mechanical properties. In conclusion, the incorporation of CO by emulsification is an effective and promising pathway to improve the properties of polysaccharide-based film.

Highly bioavailable curcumin preparation with a co-grinding and solvent-free process.

Curcumin (Cur.) is a natural product isolated from the rhizome of Curcuma longa, with a variety of biological and pharmacological activities in food and pharmaceutical products. However, curcumin's poor solubility in water greatly limits its bioavailability and clinical applications. In this study, co-grinding curcumin with food additives produced a mixture, which was evaluated for the solubility in water, dissolution, material morphology, in vivo bioavailability, cell uptake and entry mechanism. We tested 9 food additives in total and found that poloxamers performed the best. The 2 co-grinding mixtures Cur./Kolliphor® P407 and Cur./Kolliphor® P188 with high drug loading at 65.5% significantly improved the curcumin aqueous solubility, subsequently increased its intestinal epithelial cell uptake and oral bioavailability. The relative bioavailabilities for the 2 co-grinding mixtures were 309% and 163%, respectively, compared with curcumin API. Co-grinding process has a broad application prospect and is suitable for industrial production.