PMID: 

Molecules. 2019 Dec 11 ;24(24). Epub 2019 Dec 11. PMID: 31835661

Abstract Title: 

Characterization of Nine Compounds Isolated from the Acid Hydrolysate ofHsu et S. C. Cheng and Evaluation of Their In Vitro Activity towards HIV Protease.

Abstract: 

In this study, we isolated nine compounds from the acid hydrolysate of the flower buds ofHsu et S. C. Cheng and characterized their chemical structures usingH-NMR,C-NMR, and electron ionization mass spectroscopy (EI-MS). These compounds were identified asβ-sitosterol (), 5,5'-dibutoxy-2,2'-bifuran (), nonacosane-10-ol (), ethyl (3β)-3,23-dihydroxyolean-12-en-28-oate (), oleanolic acid (), ethyl caffeate (), caffeic acid (), isovanillin (), and hederagenin (), withas a new triterpene compound. Inhibitory activity against human immunodeficiency virus (HIV) protease was also evaluated for the compounds, and only ethyl caffeate, caffeic acid, and isovanillin (,, and) exhibited inhibitory effects, with ICvalues of 1.0μM, 1.5 μM, and 3.5 μM, respectively. Molecular docking with energy minimization and subsequent molecular dynamic (MD) simulation showed that ethyl caffeate and caffeic acid bound to the active site of HIV protease, while isovanillin drifted out from the active site and dissociated into bulk water during MD simulations, and most of the binding residues of HIV protease have been previously identified for HIV protease inhibitors. These results suggest that caffeic acid derivatives may possess inhibitory activities towards HIV protease other than previously reported inhibitory activities against HIV integrase, and thus ethyl caffeate and caffeic acid could be used as lead compounds in developing potential HIV protease inhibitors, and possibly even dual-function inhibitors against HIV.

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PMID: 

Biomed Res Int. 2019 ;2019:3547858. Epub 2019 Dec 10. PMID: 31886204

Abstract Title: 

Effect ofvar.Fruit on Biofilm Formed by.

Abstract: 

is an important pathogenic anaerobic bacterium that causes aspiration pneumonia. This bacterium frequently forms biofilms in the oral cavity and in respiratory tract-associated medical devices. Bacterial colonization that occurs in association with this biofilm formation is the main reason for incurable aspiration pneumonia. Thevar.(LCE) fruit has been used in folk medicine in Hokkaido, the northern part of Japan. The aim of this study was to elucidate one of the antimicrobial mechanisms of LCE methanol extract (LCEE)-the inhibitory effect of LCEE on biofilm formation byOur results show that LCEE significantly reduced biofilm formation by three differentisolates in a concentration- and time-dependent manner that were quantified by the adsorption of safranin red. When LCEE was added to biofilms already formed by, LCEE did not degrade the biofilm. However, treatment with LCEE significantly promoted the removal of existing biofilm by vibration compared to that of control. We also confirmed biofilm formation in LCEE-treatedin tracheal tubes using scanning electron microscopic (SEM) analysis. Cyanidin 3-O-glucoside (C3G), one of the components of LCE, also inhibited the formation of biofilm byin a concentration-dependent manner. Our results reveal that LCEE may be an effective antibacterial substance for-induced aspiration pneumonia because of its role in the suppression of bacterial biofilm formation in the oral cavity.

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PMID: 

J Nutr Biochem. 2019 Nov 23 ;77:108299. Epub 2019 Nov 23. PMID: 31841959

Abstract Title: 

Apple polyphenols induce browning of white adipose tissue.

Abstract: 

We and others have shown that apple polyphenols decrease adipose tissue mass. To better understand the underlying mechanisms and to expand clinical applicability, we herein examine whether apple polyphenols induce adipose thermogenic adaptations (browning) and prevent diet-induced obesity and related insulin resistance. In mice fed a standard diet, daily apple polyphenol consumption induced thermogenic adaptations in inguinal white adipose tissue (iWAT), based on increases in the expression of brown/beige adipocyte selective genes (Ucp1, Cidea, Tbx1, Cd137) and protein content of uncoupling protein 1 and mitochondrial oxidative phosphorylation enzymes. Among the upstream regulatory factors of browning, fibroblast growth factor 21 (FGF21) and peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α) levels were concomitantly up-regulated by apple polyphenols. In the primary cell culture experiment, the results did not support a direct action of apple polyphenols on beige adipogenesis. Instead, apple polyphenols increased tyrosine hydroxylase (a rate-limiting enzyme of catecholaminesynthesis) in iWAT, which activates the adipocyte thermogenic program possibly via intratissue cellular communications. In high-fat fed mice, apple polyphenols induced beige adipocyte development in iWAT, reduced fat accumulation, and increased glucose disposal rates in the glucose and insulin tolerance tests. Taken together, dietary administration of apple polyphenols induced beige adipocyte development in iWAT possibly via activation/induction of the peripheral catecholamine synthesis-FGF21-PGC-1α cascade. Results from diet-induced obese mice indicate that apple polyphenols have therapeutic potential for obesity and related metabolic disorders.

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PMID: 

Nutrients. 2019 Dec 13 ;11(12). Epub 2019 Dec 13. PMID: 31847069

Abstract Title: 

Induction of Hair Keratins Expression by an Annurca Apple-Based Nutraceutical Formulation in Human Follicular Cells.

Abstract: 

Hair disorders may considerably impact the social and psychological well-being of an individual. Recent advances in the understanding the biology of hair have encouraged the research and development of novel and safer natural hair growth agents. In this context, we have previously demonstrated-at both preclinical and clinical level-that an Annurca apple-based dietary supplement (AMS), acting as a nutraceutical, is endowed with an intense hair-inductive activity (trichogenicity), at once increasing hair tropism and keratin content. Herein, in the framework of preclinical investigations, new experiments in primary human models of follicular keratinocytes and dermal papilla cells have been performed to give an insight around AMS biological effects on specific hair keratins expression. As well as confirming the biocompatibility and the antioxidant proprieties of our nutraceutical formulation, we have proven an engagement of trichokeratins production underlying its biological effects on human follicular cells. Annurca apples are particularly rich in oligomeric procyanidins, natural polyphenols belonging to the broader class of bioflavonoids believed to exert many beneficial health effects. To our knowledge, none of the current available remedies for hair loss has hitherto shown to stimulate the production of hair keratins so clearly.

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PMID: 

J Geriatr Psychiatry Neurol. 2019 Aug 13:891988719868304. Epub 2019 Aug 13. PMID: 31409183

Abstract Title: 

Electroacupuncture Modulates Resting-State Functional Connectivity in the Default Mode Network for Healthy Older Adults.

Abstract: 

Aging involves cognitive decline and prominent alterations in brain activity. Electroacupuncture (EA), a traditional Chinese medicine approach, is demonstrated to be effective in improving cognitive function of older adults. However, the specific neural mechanism underlying this modulation effect remains unclear. In this study, we used functional magnetic resonance imaging (fMRI) to investigate whether EA could improve cognitive performance of community-dwelling older adults and whether these potential improvements are associated with the EA-induced brain functional connectivity alterations. Thirty healthy older adults were recruited and randomly assigned to the EA group and the control group. Behaviorally, we observed an EA-induced improvement in cognitive performance of older adults in the Montreal Cognitive Assessment. On a neural perspective, the EA intervention significantly increased the functional connectivity within the default mode network. Moreover, we found a positive association between the improvement in delayed memory performance and the alterations in the ventral medial prefrontal cortex-hippocampal formation connectivity in the EA group. This study extends previous findings by showing that healthy older adults exhibit neural plasticity manifested as increased functional connectivity after EA sessions, which could induce therapeutic effects in the treatment of neurodegenerative diseases.

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PMID: 

J Carcinog. 2019 ;18:4. Epub 2019 Oct 11. PMID: 31807120

Abstract Title: 

Protective potentials offruit pulp on etoposide-induced gastrointestinal toxicity in Wistar rats.

Abstract: 

BACKGROUND: Mucositis, one of the devastating consequences of chemotherapy and also limits the efficacy of the treatment. At present, there are no antimucositic agents without side effects. Hence, there is a need for better adjuvant therapy using plant or food sources. Here, we have made an attempt to study the effect of(AM) fruit pulp on etoposide-induced mucositis.MATERIALS AND METHODS: The study was conducted at Central Research Laboratory, Kasturba Medical College, Mangalore. The effect of AM fruit pulp (100 mg and 200 mg/kg body weight) on etoposide-induced mucositis was studied in Wistar rats (= 36) in comparison with normal and AM controls. Intestinal tissue was collected for histology and estimation of total antioxidants (TAO), glutathione (GSH), myeloperoxidase (MPO), and nitric oxide (NO) levels along with histological changes were studied. Statistical analysis was performed by one-way analysis of variance.RESULTS: TAO and GSH levels were found to be significantly high in the rats which received 200 mg of AM/kg body weight than 100 mg of AM/kg body weight when compared with etoposide control. The levels of inflammatory markers – MPO and NO – were found to be decreased (

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PMID: 

Zhen Ci Yan Jiu. 2019 Aug 25 ;44(8):560-5. PMID: 31475488

Abstract Title: 

[Electroacupuncture improves insomnia by down-regulating peripheral benzodiazepine receptor expression in hippocampus, and up-regulating 5-HT, 5-HIAA, TNF-α and IL-1β contents in hypothalamus in insomnia rats].

Abstract: 

OBJECTIVE: To observe the therapeutic effect of electroacupuncture (EA) at five Back-Shu points on sleep, hippocampal peripheral benzodiazepine receptor (PBR) expression and hypothalamic 5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), tumor necrosis factor alpha (TNF-α) and interleukin (IL)-1β contents in insomnia rats, so as to explore its mechanisms underlying improvement of insomnia.METHODS: Forty male SD rats were randomly divided into control, model, EA and medication (Diazepam) groups (=10 rats in each group). The insomnia model was established by intraperitoneal injection (i.p.) of para-Chlorophenylalanine (PCPA, 300 mg/kg) once daily for 2 days. EA (60 Hz, 1 mA) was applied to bilateral five Back-Shu points, i.e., Feishu (BL13), Xinshu (BL15), Ganshu (BL18), Pishu (BL20) and Shenshu (BL23) for 10 min, once daily for 6 days. Rats of the medication group were treated by gavage of Diazepam (0.92 mg/kg) once daily for 6 days. The sleep duration was recorded after i.p. of Pentobarbital Sodium (45 mg/kg). Histopathological changes of the hippocampus were displayed by H.E. staining. The contents of 5-HT, 5-HIAA, TNF-α and IL-1β in the hypothalamus were assessed by using ELISA. The expression levels of PBR mRNA and protein in the hippocampus were detected by quantitative real-time PCR, immunohistochemistry and Western blot, separately.RESULTS: Following modeling, the sleep duration was considerably shortened in rats of the model group relevant to the control group (

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PMID: 

Zhen Ci Yan Jiu. 2019 Aug 25 ;44(8):566-70. PMID: 31475489

Abstract Title: 

[Electroacupuncture intervention increases testosterone level of aged rats by activating ERK/Nrf2/HO-1 signaling of Leydig cells].

Abstract: 

OBJECTIVE: To observe the effect of electroacupuncture (EA) on anti-oxidant function of Leydig cells in aged rats with low testosterone, so as to reveal its underlying mechanism of anti-aging of male reproduction.METHODS: Eighteen 20 months old SD rats were divided into aged control, medication and EA groups(=6 in each group), and other 6 young male SD rats (2 months of age) were used as the youth control group. The rats of the youth and the aged control groups received subcutaneous injection of 0.9% normal saline (7 mg·kg·3 d) for 8 weeks, and those of the medication group received abdominal subcutaneous injection of Testosterone Propionate (7 mg·kg·3 d) for 8 weeks. EA (2 Hz/100 Hz, 1 mA) was applied to bilateral"Shenshu"(BL23) and"Guanyuan"(CV4) for 15 min, once daily for 8 weeks except the weekends. The levels of serum total testosterone (TT) and free testosterone (FT) were determined by enzyme linked immune sorbent assay (ELISA), the immunoactivity of phosphorylated extracellular signal-regulated protein kinase (p-ERK) was detected by immunohistochemistry, and the expression levels of ERK, p-ERK, nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) proteins in the testis tissues were determined by Western blot.RESULTS: Before and after the treatment, the levels of serum TT and FT in the aged control group were significantly lower than those of the youth control group (

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PMID: 

Toxicol Rep. 2019 ;6:683-691. Epub 2019 Jul 11. PMID: 31372346

Abstract Title: 

Renoprotective effects of stevia (Bertoni), amlodipine, valsartan, and losartan in gentamycin-induced nephrotoxicity in the rat model: Biochemical, hematological and histological approaches.

Abstract: 

The current study investigated the renoprotective effects of stevia, angiotensin-II type 1 receptor (AT) blocker and calcium (Ca) channel blocker in gentamycin-induced nephrotoxicity in rat models. Six groups of male Sprague-Dawley rats of eight weeks old were taken for the experiment: sham control, nephrotoxicity, treatment with amlodipine (4 mg/kg/day); stevia (200 mg/kg/day); losartan (15 mg/kg/day) and valsartan (5 mg/kg/day), accordingly. The blood sample was taken for the assessment of renal and hepatic-functional variables like serum creatinine, blood urea, BUN and SGPT, SGOT, and total serum bilirubin. Hematological parameters were also examined. Histological examination has been done on kidneys and liver. Alterations of the body weight and the organ's weight were documented. Treatment with stevia and valsartan significantly decreased serum creatinine levels. A reduction of liver enzymes, and total serum bilirubin levels were observed in all the treatment groups. Treatment with valsartan and amlodipine, remarkably and stevia, mildly reduced the renal tissue damage, inflammation, and tubular necrosis. However, the present study demonstrated that losartan treatment aggravated kidney damage by increasing proteincast, calcification, tubular necrosis, and injury. This comparison indicated that both stevia and valsartan have beneficial renoprotective effect and valsartan offers a better treatment option in renal damage over losartan.

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PMID: 

Metab Brain Dis. 2019 Sep 12. Epub 2019 Sep 12. PMID: 31515682

Abstract Title: 

Electroacupuncture ameliorates learning and memory deficits via hippocampal 5-HT1A receptors and the PKA signaling pathway in rats with ischemic stroke.

Abstract: 

Hippocampal 5-HT1A receptors and the PKA signaling pathway have been implicated in learning and memory. This study aimed to investigate whether PKA signaling mediated by 5-HT1A receptors was involved in the electroacupuncture (EA)-mediated learning and memory in a rat model of middle cerebral artery occlusion-induced cognitive deficit (MICD). Compared to no treatment or non-acupoint EA treatment, EA at DU20 and DU24 acupoints improved the neurological deficit of scores, shortened escape latency and increased the frequency of crossing the platform in the Morris water maze test. T2-weighted imaging demonstrated that the MICD rat brain lesions were mainly located in the cortex and hippocampus, and injured volumes were reduced after EA. Furthermore, we found that these behavioral changes were concomitant with the deficit of the 5HT1A and PKA signaling pathways in the hippocampus, as the activation of the 5-HT1A receptor, the reduction of PKA kinase activity, and AMPA and NMDA receptor phosphorylation occurred in the injured hippocampus at Day 14 after MICD. Additionally, EA dramatically elevated the activation of PKA. Moreover, EA significantly increased intracellular calcium concentrations regulated by the activation of NMDA receptors. Therefore, PKA kinase and NMDA receptors mediated by 5-HT1A receptors in the hippocampus might contribute to improving learning and memory during the recovery process following ischemic stroke with an EA intervention.

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