Dehydrocrenatidine inhibits head and neck cancer cells invasion and migration by modulating JNK1/2 and ERK1/2 pathway and decreases MMP-2 expression.

Head and neck cancer is associated with poor prognosis because of its highly metastatic nature. For the better management of head and neck cancer patients, it is very important to diagnose the cancer at an early stage, as well as to prevent the rapid spread of cancer either through direct invasion or lymphatic metastasis. In present study, the effect of dehydrocrenatidine, which is a beta-carboline alkaloid found in the medicinal plant Picrasma quassioides, on human head and neck cancer metastasis was investigated. The study results revealed the treatment of FaDu, SCC9, and SCC47 cells with 5, 10, and 20 µM of dehydrocrenatidine significantly decreased the motility, migration, and invasion of head and neck cancer cells. Moreover, the dehydrocrenatidine treatment significantly decreased the expression of MMP-2 and phosphorylation of ERK1/2 and JNK1/2. Additional experiments revealed that the cotreatment of dehydrocrenatidine with either ERK1/2 or JNK1/2 inhibitor caused further reduction in cancer cell motility and migration compared to that in dehydrocrenatidine treatment alone. Moreover, similar trend was observed in case of ERK1/2 and JNK1/2 phosphorylation and MMP-2 expression after the cotreatment. Taken together, the mechanism by which dehydrocrenatidine can decrease the phosphorylation of ERK1/2 and JNK1/2, follow decrease the expression of MMP-2 and inhibits head and neck cancer cells invasion and migration. This present study identifies dehydrocrenatidine as a potent antimetastatic agent that can be used clinically to improve head and neck cancer prognosis.

Seven traditional Chinese herbal extracts fermented by Lactobacillus rhamnosus provide anti-pigmentation effects by regulating the CREB/MITF/tyrosinase pathway.

Skin pigmentation is resulted from several processes, such as melanin synthesis transportation and abnormal melanin accumulation in keratinocytes. Various studies have suggested that seven traditional Chinese herbal extracts from Atractylodes macrocephala, Paeonia lactiflora, Bletilla striata, Poria cocos, Dictamnus dasycarpus, Ampelopsis japonica and Tribulus terrestris (which we collectively named ChiBai), show several protective effects toward skin-related diseases. Lactobacillus rhamnosus, a lactic acid bacterium, has been reported to treat skin inflammation and atopic dermatitis. In this study, the broth produced by the cofermentation of ChiBai with Lactobacillus rhamnosus was studied for its effects on skin pigmentation through in vitro and in vitro experiments. In the in vitro experiments, we found that the fermented broth of ChiBai (FB-ChiBai) suppressed alpha-melanocyte stimulating hormone (α-MSH)-induced melanogenesis in B16F0 murine melanoma cells without any cytotoxicity at a concentration of 0.5%. FB-ChiBai significantly attenuated melanin production, tyrosinase activities and melanogenesis-related signaling pathways. Treatment with FB-ChiBai also reduced the nuclear translocation and promoter binding activities of MITF. In the in vivo experiments, FB-ChiBai was topically applied to the dorsal skin of C57BL/6J nude mice and concurrently irradiated with UVB, three times a week for 8 weeks. The results indicated that FB-ChiBai alleviated UVB-induced hyperpigmentation by reducing epidermal hyperplasia and inhibiting the CREB/MITF/tyrosinase pathway. In conclusion, our data indicated that the anti-melanogenic effects of FB-ChiBai are mediated by the inhibition of CREB/MITF/tyrosinase signaling pathway. The findings suggest that FB-ChiBai can protect against UV-B irradiation and that it might be used as an agent in cosmetic products to protect against UVB-induced hyperpigmentation.

Extracts of Jasminum sambac flowers fermented by Lactobacillus rhamnosus inhibit H2 O2 - and UVB-induced aging in human dermal fibroblasts.

Ultraviolet (UV) irradiation is a crucial factor that leads to skin photoaging and results in increased DNA damage, oxidative stress, and collagen degradation. Jasmine flowers have been utilized as a traditional medicine in Asia to treat various diseases, including dermatitis, diarrhea, and fever. Furthermore, the fermented broth of Lactobacillus rhamnosus has been reported to exert protective effects on the skin. In the present study, jasmine flower extract was fermented with L. rhamnosus. We investigated the antioxidant and collagen-promoting effects on UVB/H2 O2 -induced HS68 dermal fibroblast cell damage. The results indicated that treatment with the fermented flower extracts of Jasminum sambac (F-FEJS) could enhance the viability of HS68 cells. Furthermore, the UVB/H2 O2 -induced excessive production of reactive oxygen species, degradation of collagen, activation of MAPKs, including P38, ERK, and JNK, and premature senescence were remarkably attenuated by F-FEJS in dermal fibroblast cells. The nuclear accumulation of p-c-jun, which is downstream of MAPK, and the inactivation of p-smad2/3, which is one of the crucial transcription factors that enhance collagen synthesis, were reversed in response to F-FEJS treatment in UVB/H2 O2 -exposed cells. Notably, the expression of antioxidant genes, such as HO-1, and the nuclear translocation of Nrf2 were further enhanced by F-FEJS in UVB/H2 O2 -treated cells. Interestingly, the F-FEJS-induced increase in ARE luciferase activity indicated the activation of Nrf2/ARE signaling. In conclusion, our findings demonstrated that F-FEJS can effectively ameliorate UVB/H2 O2 -induced dermal cell aging and may be considered a promising ingredient in skin aging therapy.

Adipose derived mesenchymal stem cells along with Alpinia oxyphylla extract alleviate mitochondria-mediated cardiac apoptosis in aging models and cardiac function in aging rats.

ETHNOPHARMACOLOGICAL RELEVANCE: The Fructus (Alpinia oxyphylla MIQ) known as Yi Zhi Ren in Chinese medicine has been used as a food and herbal medicinal substance in China for centuries; in the year 2015 Chinese Pharmacopoeia Commission reported water extracts of Alpinia oxyphyllae Fructus (AoF) as a popular medication for aging-related diseases in the form of tonic, aphrodisiac, and health-care food in south China. AIM OF THE STUDY: Adipose mesenchymal stem cells are physiologically and therapeutically associated with healthy vascular function and cardiac health. However aging conditions hinder stem cell function and increases the vulnerability to cardiovascular diseases. In this study, the effect of the anti-aging herbal medicine AoF to enhance the cardiac restorative function of adipose-derived mesenchymal stem cells (ADMSCs) in aging condition was investigated. MATERIALS AND METHODS: Low dose (0.1 µM) Doxorubicin and D-galactose (150 mg/kg/day for 8 weeks) were used to respectively induce aging in vitro and in vivo. For In vivo studies, 20 week old WKY rats were divided into Control, Aging induced (AI), AI + AoF, AI + ADMSC, AI + AoF Oral + ADMSC, and AI + AoF treated ADMSC groups. AoF (100 mg/kg/day) was administered orally and ADMSCs (1 × 106 cells) were injected (IV). RESULTS: AoF preconditioned ADMSC showed reduction in low dose Dox induced mitochondrial apoptosis and improved DNA replication in H9c2 cardiomyoblasts. In vivo experiments confirmed that both a combined treatment with AoF-ADMSCs and with AoF preconditioned ADMSCs reduced aging associated cardiac damages which was correlated with reduction in apoptosis and expression of senescence markers (P21 and ß-gal). Survival and longevity markers were upregulated up on combined administration of AoF and ADMSCs. The cardiac performance of the aging-induced rats was improved significantly in the treatment groups. AoF along with ADMSCs might activate paracrine factors to restore the performance of an aging heart. CONCLUSION: Hence, we propose that ADMSCs combined with AoF have promising therapeutic properties in the treatment of healthy aging heart.

Sodium Danshensu Inhibits Oral Cancer Cell Migration and Invasion by Modulating p38 Signaling Pathway.

Background: Oral squamous cell carcinoma (OSCC) that comprises about 90% of all oral cancer cases is associated with poor prognosis due to its highly metastatic nature. The majority of OSCC treatment options are related detrimental side-effects. Hypothesis/Purpose: The present study aimed at deciphering the effects of a bioactive phytochemical, sodium danshensu, on human oral cancer cell metastasis. Methods and Results: The treatment of FaDu and Ca9-22 cells with different doses of sodium danshensu (25, 50, and 100 µM) caused a significant reduction in cellular motility, migration, and invasion, as compared to the untreated cells. This effect was associated with a reduced expression of MMP-2, vimentin and N-cadherin, together with an enhanced expression of E-cadherin and ZO-1. Further investigation on the molecular mechanism revealed that treatment with sodium danshensu caused significant reduction in p38 phosphorylation; however, phosphorylation of ERK1/2 significantly decreased only in FaDu cells, whereas p-JNK1/2 did not show any alteration. A combination of p38 and JNK1/2 inhibitors with sodium danshensu also reduced the migration in the FaDu and Ca9-22 cell lines. Conclusion: Collectively, the present study findings reveal that sodium danshensu execute anti-metastatic effect by suppressing p38 phosphorylation in human oral cancer. The study identifies sodium danshensu as a potential natural anticancer agent that can be used therapeutically to manage highly metastatic OSCC.

Parkinson's disease a futile entangle of Mankind's credence on an herbal remedy: A review.

Parkinson's disease (PD) is a disease of the human nervous system with an onset, in the sixth and seventh decades of the human life. Chiefly perceived as progressive degeneration of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc) with the ensued loss of dopamine in the striatum and the presence of Lewy bodies, consisting of α-synuclein agglomeration. In which the neuronal bridge between substantia nigra and striatum plays an advent role in the motor system. Dilapidation of these neurons results in dopamine depletion which in-turn makes hay to PD. Eventually, the etiology and pathogenesis of PD were still on a hike of dilemma. Traditional Chinese medicine (TCM), including Chinese herbal remedies, acupuncture, and manipulative therapies, is commonly used as an adjunctive therapy in different diseases, particularly neurological diseases, in Asian countries. Additionally, TCM might improve the prognoses and the quality of life of patients with PD because it induces less adverse drug reactions. The present review describes research on the various neuroprotective components and herbal extracts from herbal medicines in the context of addressing the effects of PD.

Danshen (Salvia miltiorhiza) inhibits Leu27 IGF-II-induced hypertrophy in H9c2 cells.

In this study, we used ICI 182 780 (ICI), an estrogen receptor (ER) antagonist, to investigate the estrogenic activity of Danshen, and to further explored whether Danshen extract can block Leu27IGF-II-induced hypertrophy in H9c2 cardiomyoblast cells. We first used an IGF-II analog Leu27IGF-II, which specifically activates IGF2R signaling cascades and induces H9c2 cardiomyoblast cell hypertrophy. However, Danshen extract completely inhibited Leu27IGF-II-induced cell size increase, ANP and BNP hypertrophic marker expression, and IGF2R induction. We also observed that Danshen extract inhibited calcineurin protein expression and NFAT3 nuclear translocation, leading to suppression of Leu27IGF-II-induced cardiac hypertrophy. Moreover, the anti-Leu27IGF-II-IGF2R signaling effect of Danshen was totally reversed by ICI, which suggest the cardio protective effect of Danshen is mediated through estrogen receptors. Our study suggests that, Danshen exerts estrogenic activity, and thus, it could be used as a selective ER modulator in IGFIIR induced hypertrophy model.

Bioactive peptides attenuate cardiac apoptosis in spontaneously hypertensive rat hearts through activation of autophagy and mitochondrial biogenesis pathway.

Alcalase potato protein hydrolysate (APPH) might have a very important role in therapeutic effects. This study aims to examine the beneficial effects of bioactive peptides (DIKTNKPVIF [DI] and IF) from APPH supplement in the regulation of cardiac apoptosis, autophagy, and mitochondrial biogenesis pathway in spontaneously hypertensive rats (SHR). We have investigated ejection fraction, fractional shortening, Tunel assay, apoptosis, autophagy, and mitochondrial biogenesis pathway marker expression to show the efficacy of bioactive peptides in an SHR model. Bioactive peptides significantly upregulate ejection fraction and fractional shortening in SHR rats. SHR rats exhibited higher protein expression of apoptotic markers such as BAD, cytochrome c, and caspase 3. Finally, the bioactive peptides upregulate survival proteins (p-AKT/p-PI3K), autophagy (Beclin1/LC3B), and mitochondrial biogenesis (p-AMPKα/SIRT1/PGC1α/p-Foxo3a/Nrf2/CREB) marker expressions compared with the SHR groups. In summary, the bioactive peptides protect the heart tissues through the activation of autophagy and mitochondrial biogenesis pathway and thereby attenuate cardiac apoptosis in a spontaneously hypertensive rat model.

Dipeptide IF prevents the effects of hypertension-induced Alzheimer's disease on long-term memory in the cortex of spontaneously hypertensive rats.

Hypertension (HTN) is one of the most prevalent chronic conditions; it can damage blood vessels and rupture blood vessels can trap in small vessels. This blockage can prevent blood flow and oxygen delivery to brain cells and can result in Alzheimer's disease (AD). HTN- and AD-mediated long-time memory loss and its treatment remain poorly understood. Plant-derived natural compounds are alternative solutions for effectively treating diseases without any side effects. This study revealed that bioactive peptides extracted from potato hydrolysis suppress HTN-mediated long-term memory (LTM) loss and cell apoptosis, thus improving memory formation and neuronal cell survival in the spontaneously hypertensive rat (SHR) rat model. SHR rats were treated with bioactive peptide IF (10 mg/kg orally) and angiotensin-converting enzyme inhibitors (5 mg/kg orally). In this study, we evaluated the molecular expression levels of BDNF-, GluR1-, and CREB-mediated markers protein expression in 24-week-old SHR rats. The study result showed that HTN-induced AD regulated long-term memory (LTM) loss and neuronal degeneration in the SHR animals. The bioactive peptide-treated animals showed an elevated level of survival proteins. Bioactive peptide IF activate CREB-mediated downstream proteins to regulate synaptic plasticity and neuronal survival in the SHR rat model.