Tyrosinase is a multi-copper enzyme which is widely distributed in different organisms and plays an important role in the melanogenesis and enzymatic browning. Therefore, its inhibitors can be attractive in cosmetics and medicinal industries as depigmentation agents and also in food and agriculture industries as antibrowning compounds. For this purpose, many natural, semi-synthetic and synthetic inhibitors have been developed by different screening methods to date. This review has focused on the tyrosinase inhibitors discovered from all sources and biochemically characterised in the last four decades.

https://northumbria-test.eprints-hosting.org/id/document/268389

A comprehensive review on tyrosinase inhibitors.

Agastache rugosa (Fisch. & C.A.Mey.) Kuntze (Korean mint) is used to treat diverse types of human disorders in traditional medicine. In recent years, its non-fermented leaf extract (ARE) has been shown to possess protective properties against ultraviolet-B (UV-B) radiation-induced photooxidative stress. The present work aimed to examine whether probiotic bacterial fermentation would potentiate the skin anti-photoaging activity of ARE or not, by comparing the protective properties of ARE and corresponding fermented extract (ARE-F) against UV-B radiation-induced photooxidative stress in HaCaT keratinocytes. ARE-F was produced from ARE by the fermentation with Lactobacillus rhamnosus HK-9, a type of Gram-positive probiotic bacterial strain. Anti-photoaging activities were evaluated by analyzing reactive oxygen species (ROS), promatrix metalloproteinases (proMMPs), total glutathione (GSH) and total superoxide dismutase (SOD) in UV-B-irradiated HaCaT keratinocytes. Antiradical activity was determined using 2,2-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging assay. ARE-F contained higher attenuating activity on the UV-B-induced ROS generation than ARE. Similarly, ARE-F was able to diminish the UV-B-induced proMMP-9 and -2 more effectively than ARE. ARE-F displayed higher tendencies to augment the UV-B-reduced total GSH content and SOD activity than ARE. However, there were no significant difference between ARE and ARE-F in ABTS radical scavenging activities. The findings suggest that the UV-B radiation-protective activity of ARE is enhanced by probiotic bacterial fermentation, which might improve the therapeutic and cosmetic values of A. rugosa leaves.

/pdf/probiotic-fermentation-augments-the-skin-anti-photoaging-4f37ffb711.pdf

Probiotic fermentation augments the skin anti-photoaging properties of Agastache rugosa through up-regulating antioxidant components in UV-B-irradiated HaCaT keratinocytes.

Catalysis-based specific detection and inhibition of tyrosinase and their application.

Agastache rugosa is used as a Korean traditional medicine to treat gastric diseases. However, the active ingredients and pharmacological targets of A. rugosa are unknown. In this study, we aimed to reveal the pharmacological effects of A. rugosa on gastritis by combining a mice model and a network pharmacology method. The macrophage and gastritis-induced models were used to evaluate the pharmacological effects of A. rugosa. The results show that A. rugosa relieved mucosal damage induced by HCl/EtOH in vivo. Network analysis identified 99 components in A. rugosa; six components were selected through systematic screening, and five components were linked to 45 gastritis-related genes. The main components were acacetin and luteolin, and the identified core genes were AKT serine/threonine kinase 1 (AKT1), nuclear factor kappa B inhibitor alpha (NFKBIA), and mitogen-activated protein kinase-3 (MAPK3) etc. in this network. The network of components, target genes, protein-protein interactions, and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway was closely connected with chemokines and with phosphoinositide 3-kinase-Akt (PI3K/AKT), tumor-necrosis-factor alpha (TNFα), mitogen-activated protein kinase, nuclear factor kappa B, and Toll-like receptor (TLR) pathways. In conclusion, A. rugosa exerts gastro-protective effects through a multi-compound and multi-pathway regulatory network and holds potential for treating inflammatory gastric diseases.

https://www.mdpi.com/2218-273X/10/9/1298/pdf

Pharmacological Effects of Agastache rugosa against Gastritis Using a Network Pharmacology Approach.

Anacamptis pyramidalis (L.) Rich. forms part of the Orchidaceae family that is highly valued for its horticultural as well as therapeutic benefits. The present study set out to investigate the inhibitory activity of A. pyramidalis tubers against key biological targets for the management of type 2 diabetes, Alzheimer disease, and skin hyperpigmentation. In addition, the antioxidant potential of the extracts was also assessed using multiple methods. The detailed phytochemical profiles of the extracts were determined using high-performance liquid chromatography. Based on qualitative phytochemical fingerprint, a network pharmacology analysis was conducted as well. Parishin was identified from the water extract only, whereas gastrodin and caffeic acid derivatives were present in the methanol extract. The methanol extract exhibited high inhibitory activity against tyrosinase (69.69 mg kojic acid equivalent/g extract), α-amylase (15.76 mg acarbose equivalent/g extract), and α-glucosidase (20.07 mg acarbose equivalent/g extract). Similarly, the methanol extract showed highest antioxidant potential (22.12, 44.23, 45.56, and 29.38 mg Trolox equivalent/g extract, for 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), CUPric Reducing Antioxidant Capacity (CUPRAC), and Ferric Reducing Antioxidant Power (FRAP) assays, respectively). Finally, the results of network pharmacology analysis, besides corroborating traditional uses of plant extracts in the management of cold and flu, confirmed a direct involvement of identified phytochemicals in the observed enzyme inhibitory effects, especially against tyrosinase, α-amylase, and α-glucosidase. Furthermore, based on the results of both colorimetric assays and network pharmacology analysis related to the activity of A. pyramidalis extracts and identified phytocompounds on enzymes involved in type 2 diabetes, a docking study was conducted in order to investigate the putative interactions of oxo-dihydroxy octadecenoic acid trihydroxy octadecenoic acid against aldose reductase, peroxisome proliferator-activated receptor (PPAR)-α, dipeptidyl peptidase (DPP)-IV, and α-glucosidase. Docking analysis suggested the inhibitory activity of these compounds against the aforementioned enzymes, with a better inhibitory profile shown by oxo-dihydroxy octadecenoic acid. Overall, the present findings supported the rationale for the use of A. pyramidalis as source of bioactive metabolites and highlight, today more than ever, for the strong necessity of linkage strategy between wild resource valorization and conservation policy.

https://www.mdpi.com/1420-3049/25/10/2422/pdf

Phytochemical Analysis, Network Pharmacology and in Silico Investigations on Anacamptis pyramidalis Tuber Extracts.

SummaryBackground
This work presents the first report that A. rugosa could have tyrosinase and melanogenesis inhibition and that its activities also be improved by fermentation with Lactobacillus rhamnosus and Lactobacillus paracasei. It was found that the tyrosinase and melanogenesis inhibition was correlated with antioxidant activity of acacetin, the major biologically active substances in A. rugosa.

Aims
we pursued an improvement in tyrosinase and melanogenesis inhibition of A. rugosa extract by fermentation process.

Methods
A. rugosa was extracted by lactic acid fermentation process; we measured antioxidant activities and tyrosinase and melanogenesis inhibition of A. rugosa extracts.

Result
In particular, reducing power of the extract from fermentation process (FE) was measured as 0.562 (O.D.), whereas reducing power of the extracts from 70% ethanol extraction (EE) was lower than the FE as 0.496 (O.D.). Polyphenols and flavonoids in the FE were higher than the EE: 69.3 mg/g vs. 60.5 mg/g, and 187 mg/g vs. 138 mg/g. The FE was estimated as 51.04% tyrosinase inhibition and 41.88% for the EE. Similarly, melanin inhibition in melanocyte B16F10 was observed as 66.60% vs. 42.23% for the FE and EE. The increase in tyrosinase and melanogenesis inhibition activity was confirmed by high elution of acacetin through fermentation process such as 289.97 mg/100 g vs. 198.04 mg/100 g in the FE and EE.

Conclusion
These results indicate that tyrosinase and melanogenesis inhibition activities of the extracts should be associated with antioxidant activity because acacetin is known to have strong antioxidant activity, which can also positively affect whitening activities.

Hee Souk Kwon

Papers

Effect of inhibition on tyrosinase and melanogenesis of Agastache rugosa Kuntze by lactic acid bacteria fermentation