Isoliquiritigenin (ISL), a flavonoid component from the hydrolysis products of licorice root. It has been reported that ISL inhibited melanogenesis by suppressing the tyrosinase activity in human melanocytes. Recently, ISL was found to induce melanin degradation in human epidermal keratinocytes. However, the role of ISL in pigmentation is not fully understood. In the current study, we aimed to investigate the effects of ISL on pigmentation, and further explored the underlying mechanism. Our results suggested that ISL suppressed basal and α‐MSH‐, ACTH‐ and UV‐induced melanin synthesis, in addition to inhibiting melanocyte dendricity and melanosome transport. ISL played these roles mainly by activating the extracellular signal‐regulated protein kinase pathway. Once activated, it induced microphthalmia‐associated transcription factor degradation and decreased the expression of tyrosinase, TRP‐1, DCT, Rab27a and Cdc42, finally inhibited melanogenesis, melanocyte dendricity and melanosome transport. Our findings suggested that ISL exhibited no cytotoxicity in our research, it may prove quite useful as a safer natural skin‐whitening agent.

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Background Major depressive disorder (MDD) is a severe mental disorder related to the deficiency of monoamine neurotransmitters, particularly to abnormalities of 5-HT (5-hydroxytryptamine, serotonin) and its receptors. Our previous study suggested that acute treatment with a novel curcumin derivative J147 exhibited antidepressant-like effects by increasing brain derived neurotrophic factor (BDNF) level in the hippocampus of mice. The present study expanded upon our previous findings and investigated the antidepressant-like effects of sub-acute treatment of J147 for 3 days in male ICR mice and its possible relevancy to 5-HT 1A and 5-HT 1B receptors and downstream cAMP-BDNF signaling. Methods J147 at doses of 1, 3, and 9 mg/kg (via gavage) was administered for 3 days, and the anti-immobility time in the forced swimming and tail suspension tests (FST and TST) was recorded. The radioligand binding assay was used to determine the affinity of J147 to 5-HT 1A and 5-HT 1B receptor. Moreover, 5-HT 1A or 5-HT 1B agonist or its antagonist was used to determine which 5-HT receptor subtype is involved in the antidepressant-like effects of J147. The downstream signaling molecules such as cAMP, PKA, pCREB, and BDNF were also measured to determine the mechanism of action. Results The results demonstrated that sub-acute treatment of J147 remarkably decreased the immobility time in both the FST and TST in a dose-dependent manner. J147 displayed high affinity in vitro to 5-HT 1A receptor prepared from mice cortical tissue and was less potent at 5-HT 1B receptor. These effects of J147 were blocked by pretreatment with a 5-HT 1A antagonist NAD-299 and enhanced by a 5-HT 1A agonist 8-OH-DPAT. However, 5-HT 1B receptor antagonist NAS-181 did not appreciably alter the effects of J147 on depression-like behaviors. Moreover, pretreatment with NAD-299 blocked J147-induced increases in cAMP, PKA, pCREB, and BDNF expression in the hippocampus, while 8-OH-DPAT enhanced the effects of J147 on these proteins’ expression. Conclusion The results suggest that J147 induces rapid antidepressant-like effects during a 3-day treatment period without inducing drug tolerance. These effects might be mediated by 5-HT 1A -dependent cAMP/PKA/pCREB/BDNF signaling.

Three novel 14-membered cyclopeptide alkaloids, justicianenes B-D (1-3), were isolated from the EtOH extract of the whole plant of Justicia procumbens L., and their structures were determined on the basis of detailed NMR spectroscopic data and the absolute stereochemistry of the ring-bonded α-amino acids in the cyclopeptide alkaloids were determined by ECD spectra. The isolated compounds were evaluated for their in vitro cytotoxicity against human cancer cell lines, including brest cancer MCF-7, cervix carcinoma HeLa, lung cancer A549 and H460, and diphyllin (14) showed moderate cytotoxicity against the HeLa, A549 and H460 cells with IC 50 of 9.13, 23.12, 42.34 µM, respectively, justicianene D showed weak cytotoxicity against the MCF-7 cell with inhibition rate of 50% at the concentration of 90 µM.

Osteoporosis is a severe bone disease characterized by a decrease in the density and structure of bones, with high risks of fractures. Pilose antler peptide (PAP), extracted and purified from deer antlers, can promote regeneration and fracture healing, and strengthen sinews and bone. To determine whether PAP can promote osteoblast development and to elucidate the molecular mechanisms underlying its functions, the present study investigated the effects of PAP on osteoblast proliferation, differentiation and mineralization, and the role of the insulin signaling pathway using MTT assay, alkaline phosphatase activity assay, western blot analysis and reverse transcription-quantitative PCR. The present results suggested that PAP promoted osteoblast proliferation, differentiation and mineralization in vitro via the insulin signaling pathway. The effect of PAP on insulin signaling in osteoblasts may be mediated via the ERK pathway and partially by the PI3K/Akt pathway. The present results indicated that PAP could potentially be developed as an alternative treatment strategy for bone diseases related to diabetes characterized by insulin signaling impairment.

Protoporphyrin IX (PPIX) is a heterocyclic organic compound that is the last intermediate in the heme biosynthetic pathway. PPIX, due to its photodynamic effects, is utilized in the treatment of skin diseases. Furthermore, PPIX has been utilized as a melanogenesisstimulating agent in various studies. However, the exact function and mechanism underlying PPIX action in melanocytes remain to be elucidated. In the present study, we sought to further investigate how PPIX affects melanocyte melanogenesis, and whether PPIX is involved in melanin transport. Our findings demonstrated that PPIX increased melanocyte dendricity and melanosome transport, in addition to increasing melanogenesis. PPIX functions primarily by activating the guanylate cyclase (GC) and cyclic guanosine 3', 5'-monophosphate/protein kinase G (cGMP/PKG) signaling pathways. Once activated, these pathways increase tyrosinase activity and the expression of microphthalmiaassociated transcription factor (MITF), tyrosinase, tyrosinase-related protein-1 and-2 (TRP-1 and TRP-2), myosin Va, melanophinin, Ras-related protein Rab-27A (Rab27a), and cell division cycle 42 (Cdc42), promoting melanogenesis, melanocyte dendricity, and melanosome transport. Furthermore, the melanogenic effects of PPIX were confirmed in vivo in a zebrafish model system. Our results indicate that PPIX is not cytotoxic and may, thus, be utilized as a pigmentation enhancer.

FGIN-1-27 is a synthetic mitochondrial diazepam binding inhibitor receptor (MDR) agonist that has demonstrated pro-apoptotic, anti-anxiety, and steroidogenic activity in various studies. Here we report, for the first time, the anti-melanogenic efficacy of FGIN-1-27 in vitro and in vivo. FGIN-1-27 significantly inhibited basal and α-melanocyte-stimulating hormone (α-MSH)-, 1-Oleoyl-2-acetyl-sn-glycerol (OAG)- and Endothelin-1 (ET-1)-induced melanogenesis without cellular toxicity. Mushroom tyrosinase activity assay showed that FGIN-1-27 did not directly inhibit tyrosinase activity, which suggested that FGIN-1-27 was not a direct inhibitor of tyrosinase. Although it was not capable of modulating the catalytic activity of mushroom tyrosinase in vitro, FGIN-1-27 downregulated the expression levels of key proteins that function in melanogenesis. FGIN-1-27 played these functions mainly by suppressing the PKA/CREB, PKC-β, and MAPK pathways. Once inactivated, it decreased the expression of MITF, tyrosinase, TRP-1, TRP-2, and inhibited the tyrosinase activity, finally inhibiting melanogenesis. During in vivo experiments, FGIN-1-27 inhibited the body pigmentation of zebrafish and reduced UVB-induced hyperpigmentation in guinea pig skin, but not a reduction of numbers of melanocytes. Our findings indicated that FGIN-1-27 exhibited no cytotoxicity and inhibited melanogenesis in both in vitro and in vivo models. It may prove quite useful as a safer skin-whitening agent.

Growing bodies of data show that psychological stress can be associated with hair loss and vitiligo. Researchers have revealed that stress could indeed inhibit hair growth in vivo, but the relationship between chronic stress and melanogenesis remains unknown. In this study, we established two types of stress models, chronic restraint stress (CRS) and chronic unpredicted mild stress (CUMS) mice models, and explored the possible role of stress in mice hair follicle melanogenesis. We found that stress changed hippocampal morphology, decreased 5-HT level in brain and skin and down-regulated 5-HT1A receptor expression in hippocampal CA1 region and skin. The alterations of 5-HT and 5-HT1A receptor might be a threshold of central stress to associate with the behaviour changes. Both two stresses caused cellular damage of melanocytes and inhibition of keratinocytes proliferation in HF, which made the synthetic pigment loss. CRS which was considered primarily as a "psychological" stressor had the lower melanin production in HF, as well as the level of 5-HT in skin was down-regulated more than those in CUMS group.