Assoc.Prof. Parinya Noisa

Year	Month	Title	Journal
2023	November	Cordycepin, a bioactive compound from Cordyceps spp., moderates Alzheimerâ€™s disease-associated pathology via anti-oxidative stress and autophagy activation Soraksa N.; Heebkaew N.; Promjantuek W.; Kunhorm P.; Kaokean P.; Chaicharoenaudomung N.; Noisa P.	Journal of Asian Natural Products Research
Abstract: Alzheimerâ€™s causes cognitive dysfunction. This study investigated the neuro-promoting effects of cordycepin on amyloid-beta precursor protein (APP) synthesis in human neuroblastoma SH-SY5Y cells. Cordycepin was found to boost SH-SY5Y cell proliferation and decreased AD pathology. APP, PS1, and PS2 were downregulated whereas ADAM10 and SIRT1 were upregulated by cordycepin. Cordycepin also reduced APP secretion in a dose-dependent manner. Cordycepin alleviated oxidative stress by the upregulation of GPX and SOD, as well as autophagy genes (LC3, ATG5, and ATG12). Cordycepin activity was also found to be SIRT1-dependent. Therefore, cordycepin may relieve the neuronal degeneration caused by APP overproduction, and oxidative stress. Â© 2023 Informa UK Limited, trading as Taylor & Francis Group. Keyword: Alzheimerâ€™s disease; autophagy; Cordycepin; oxidative stress; SIRT1 Scopus Link: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85171895982&doi=10.1080%2f10286020.2023.2258797&partnerID=40&md5=39d311be80db3b294a55f92f928c8918 DOI: 10.1080/10286020.2023.2258797
2023	November	Cordycepin Enhances the Cytotoxicity of Human Natural Killer Cells against Cancerous Cells Chaicharoenaudomrung N.; Kunhorm P.; Noisa P.	Biological and Pharmaceutical Bulletin
Abstract: Cancer treatment with natural killer (NK) cell immunotherapy is promising. NK cells can recognize and kill cancer cells without sensitization, making them a potential cancer treatment alternative. To improve clinical efficacy and safety, more research is needed. Enhancing NK cell function improves therapeutic efficacy. Due to its potent apoptosis induction, Cordycepin, a bioactive compound from Cordyceps spp., inhibits cancer cell growth. Cordycepin has immunoregulatory properties, making it a promising candidate for combination therapy with NK cell-based immunotherapy. Cordycepin may enhance NK cell function and have clinical applications, but more research is needed. In this study, cordycepin treatment of NK-92 MI cells increased THP-1 and U-251 cell cytotoxicity. Cordycepin also significantly increased the mRNA expression of cytokine-encoding genes, including tumour necrosis factor (TNF), interferon gamma (IFNG), and interleukin 2 (IL2). NK-92 MI cells notably secreted more IFNG and granzyme B. Cordycepin also decreased CD27 and increased CD11b, CD16, and NKG2D in NK-92 MI cells, which improved its anti-cancer ability. In conclusion, cordycepin could enhance NK cell cytotoxicity against cancerous cells for the first time, supporting its use as an alternative immunoactivity agent against cancer cells. Further studies are needed to investigate its efficacy and safety in clinical settings. 2023 The Pharmaceutical Society of Japan. Keyword: cancerous cell; Cordycepin; Cordyceps; immunotherapy; natural killer (NK) cell; NK-92 MI Scopus Link: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85169650481&doi=10.1248%2fbpb.b23-00221&partnerID=40&md5=e14e3aa9327ef76a3249ee38ab66d17f DOI: 10.1248/bpb.b23-00221
2023		The neuroprotective effects of the combined extract of mulberry fruit and mulberry leaf against hydrogen peroxide-induced cytotoxicity in SH-SY5Y Cells Mairuae N., Palachai N., Noisa P.	BMC Complementary Medicine and Therapies
Abstract: The prevalence of dementia is increasing, and most of the causes are related to neuronal cell death. Unfortunately, no effective strategy is available for protecting against this condition. Based on the use of the synergistic concept together with the positive modulation effect of both mulberry fruit and mulberry leaf on dementia, we hypothesized that the combined extract of mulberry fruit and mulberry leaf (MFML) should mitigate neuronal cell death. Neuronal cell damage was induced in SH-SY5Y cells by exposure to hydrogen peroxide at a dose of 200 μM. SH-SY5Y cells were given MFML at doses of 62.5 and 125 μg/mL before induced cytotoxicity. Then, the cell viability was determined via MTT assay, and the possible underlying mechanisms were investigated via the alterations of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), malondialdehyde (MDA), nuclear factor-κB (NF-κB), and tumor necrosis factor-alpha (TNF-α), together with apoptotic factors including (B-cell lymphoma 2) BCL2, Casapase-3 and Caspase-9. The results showed that MFML significantly enhanced cell viability. It also significantly decreased MDA level, NF-κB, TNF-α, Casapase-3, Caspase-9, but increased SOD, GSH-Px and BCL2. These data demonstrated the neuroprotective effect of MFML. The possible underlying mechanisms might occur partly via the improvement of the inappropriate apoptotic mechanisms via BCL2, Casapase-3 and Caspase-9 together with the decrease in neurodegeneration induced by the reduction of inflammation and oxidative stress. In conclusion, MFML is a potential neuroprotectant candidate against neuronal cell injury. However, toxicity, animal studies, and clinical trials are essential to confirm these benefits. © 2023, The Author(s). Keyword: Mulberry fruit; Mulberry leaf; Neuronal cells; SH-SY5Y Scopus Link: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85152382533&doi=10.1186%2fs12906-023-03930-z&partnerID=40&md5=b10f613355fc8aed693e8d3d75bf961e DOI: 10.1186/s12906-023-03930-z
2023		Development of an animal-free nitrogen source for the liquid surface culture of Cordyceps militaris Sripilai K., Chaicharoenaudomrung N., Phonchai R., Chueaphromsri P., Kunhorm P., Noisa P.	Letters in applied microbiology
Abstract: Cordyceps militaris is a medicinal mushroom in Asia in the 21st century, which cordycepin is a significant bioactive compound. This study, investigated the effect of culture conditions and vegetable seed extract powder as a supplementary source of animal-free nitrogen on the production of cordycepin by C. militaris in liquid surface culture. The highest cordycepin production was observed under soybean extract powder (SBEP) conditions, and 80 g L-1 of SBEP supplementation increased cordycepin production to 2.52 g L-1, which was greater than the control (peptone). Quantitative polymerase chain reaction was used to examine the transcription levels, and the results showed that supplementing with SBEP 80 g L-1 significantly increased the expression of genes associated with the carbon metabolic pathway, amino acid metabolism, and two key genes involved in the cordycepin biosynthesis (cns1 and NT5E) compared to peptone-supplemented culture. Under optimal culture conditions, the model predicted a maximum response of cordycepin production of 2.64 g L-1 at a working volume of 147.5 ml, an inoculum size of 8.8% v/v, and a cultivation time of 40.0 days. This optimized culture condition could be used to increase cordycepin production in large-scale bioreactors. Additional research can be conducted to assess the economic viability of this process. © The Author(s) 2023. Published by Oxford University Press on behalf of Applied Microbiology International. Keyword: Cordyceps militaris; animal-free nitrogen sources; cordycepin; liquid surface culture; vegetable seed Scopus Link: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85159253952&doi=10.1093%2flambio%2fovad053&partnerID=40&md5=642b5af2530e5b8774d32c26bc4b7146 DOI: 10.1093/lambio/ovad053
2023		Cordycepin Enhances SIRT1 Expression and Maintains Stemness of Human Mesenchymal Stem Cells Chueaphromsri P., Kunhorm P., Phonchai R., Chaicharoenaudomrung N., Noisa P.	In Vivo
Abstract: Background/Aim: Mesenchymal stem cells (MSCs) have been employed for therapeutic applications of various degenerative diseases. However, the major concern is MSC aging during the in vitro cultivation. Thus, the approach to delay MSC aging was examined in this research by focusing on the expression of Sirtuin 1 (SIRT1), a key anti-aging marker. Materials and Methods: Cordycepin, a bioactive compound derived from Cordyceps militaris, was used to up-regulate SIRT1 and maintain stemness of MSCs. Upon treatment with cordycepin, MSCs were investigated for cell viability, doubling time, key gene/protein expression, galactosidase-associated senescence assay, relative telomere length, and telomerase expression. Results: Cordycepin significantly increased the expression of SIRT1 in MSCs by activating the adenosine monophosphate activated protein kinase (AMPK)-SIRT1 signalling pathway. Moreover, cordycepin maintained the stemness of MSCs by deacetylating SRY-box transcription factor 2 (SOX2) via SIRT1, and cordycepin delayed cellular senescence and aging of MSCs by enhancing autophagy, inhibiting the activity of senescence-associated-galactosidase, maintaining proliferation rate, and increasing telomere activity. Conclusion: Cordycepin could be used to increase SIRT1 expression in MSCs for anti-aging applications. © 2023 International Institute of Anticancer Research. All rights reserved. Keyword: anti-aging; Cordycepin; mesenchymal stem cells; SIRT1 Scopus Link: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85149543461&doi=10.21873%2finvivo.13118&partnerID=40&md5=e090fd33e83bfcaca6dac1510ee7ca83 DOI: 10.21873/invivo.13118
2023		Cordycepin-induced Keratinocyte Secretome Promotes Skin Cell Regeneration Kunhorm P., Chaicharoenaudomrung N., Noisa P.	In Vivo
Abstract: Background/Aim: Skin regeneration is the intrinsic ability to repair damaged skin tissues to regaining skin wellbeing. Processes of wound healing, a major part of skin regeneration, involve various types of cells, including keratinocytes and dermal fibroblasts, through their autocrine/paracrine signals. The releasable factors from keratinocytes were reported to influence dermal fibroblasts behavior during wound-healing processes. Here, we developed a strategy to modulate cytokine components and improve the secretome quality of HaCaT cells, a nontumorigenic immortalized keratinocyte cell line, via the treatment of cordycepin, and designated as cordycepin-induced HaCaT secretome (CHS). Materials and Methods: The bioactivities of CHS were investigated in vitro on human dermal fibroblasts (HDF). The effects of CHS on HDF proliferation, reactive oxygen species-scavenging, cell migration, extracellular matrix production and autophagy activation were investigated by 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl tetrazolium bromide cell viability assay, dichloro-dihydro-fluorescein diacetate, the wound-healing assay, reverse transcription polymerase chain reaction and immunofluorescent microscopy. Finally, Proteome Profiler™ Array was used to determine the composition of the secretome. Results: CHS induced fibroblast proliferation/migration, reactive oxygen species-scavenging property, regulation of extracellular matrix synthesis, and autophagy activation. Such enhanced bioactivities of CHS were related to the increase of some key cytokines, including C-X-C motif chemokine ligand 1, interleukin 1 receptor A, interleukin 8, macrophage migration-inhibitory factor, and serpin family E member 1. Conclusion: These findings highlight the implications of cordycepin alteration of the cytokine profile of the HaCaT secretome, which represents a novel biosubstance for the development of wound healing and skin regeneration products. © 2023 International Institute of Anticancer Research. All rights reserved. Keyword: Cordycepin; dermal fibroblast; keratinocyte; secretome; skin regeneration Scopus Link: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85149491849&doi=10.21873%2finvivo.13116&partnerID=40&md5=1469cbdfbf8a8dc42f47bd5e7537d3a8 DOI: 10.21873/invivo.13116
2023		Hybrid Cyanine/Methotrexate Nanoparticles for Synergistic PDT/Chemotherapy of Breast Cancer Muangsopa P., Chansaenpak K., Kampaengsri S., Saetiew J., Noisa P., Meemon P., Kamkaew A.	ACS Applied Bio Materials
Abstract: Typically, nanomedicine was prepared using a nanocarrier to load cargo for specific purposes. In this work, a carrier-free nanosystem for imaging and photodynamic (PDT)/chemo combination therapy was developed using simple self-assembly of a dye and a chemotherapeutic agent. The resulting nanoparticles (I2-IR783/MTX@NPs) exhibited a spherical morphology with a size of 240.6 ± 2.5 nm. I2-IR783/MTX@NPs had substantial internalization in 4T1 murine breast cancer cells and showed a synergistic anticancer effect after NIR light irradiation. Additionally, the 3D tumor model exhibits the same phototoxicity of nanoparticles as a 2D cell culture. The PDT efficiency of the nanosystem in the physiological environment was confirmed by the detection of intracellular reactive oxygen species as well as the live/dead viability/cytotoxicity assay following NIR light exposure. In addition, optical coherence tomography (OCT) was used as an alternative tool to monitor the response after treatment. Therefore, I2-IR783/MTX@NPs show great potential use in theranostic application for breast cancer PDT-chemotherapy. © 2023 American Chemical Society Keyword: heptamethine cyanine; methotrexate; optical coherence tomography; photodynamic therapy; self-assembly; synergistic treatment Scopus Link: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85146134494&doi=10.1021%2facsabm.2c00893&partnerID=40&md5=4cc628ec1b39ebd4f8e44446fac372b1 DOI: 10.1021/acsabm.2c00893
2023		Enhancing Neurological Competence of Nanoencapsulated Cordyceps/Turmeric Extracts in Human Neuroblastoma SH-SY5Y Cells Kaokaen P., Sorraksa N., Phonchai R., Chaicharoenaudomrung N., Kunhorm P., Noisa P.	Cellular and Molecular Bioengineering
Abstract: Introduction: Neurological diseases, including Alzheimer's, Parkinson's diseases, and brain cancers, are reportedly caused by genetic aberration and cellular malfunction. Herbs with bioactive compounds that have anti-oxidant effects such as cordyceps and turmeric, are of interest to clinical applications due to their minimal adverse effects. The aim of study is to develop the nanoencapsulated cordyceps and turmeric extracts and investigate their capability to enhance the biological activity and improve neuronal function. Methods: Human neuroblastoma SH-SY5Y cells were utilized as a neuronal model to investigate the properties of nanoencapsulated cordyceps or turmeric extracts, called CMP and TEP, respectively. SH-SY5Y cells were treated with either CMP or TEP and examined the biological consequences, including neuronal maturation and neuronal function. Results: The results showed that both CMP and TEP improved cellular uptake efficiency within 6 h by 2.3 and 2.8 times, respectively. Besides, they were able to inhibit cellular proliferation of SH-SY5Y cells up to 153- and 218-fold changes, and increase the expression of mature neuronal markers (TUJ1, PAX6, and NESTIN). Upon the treatment of CMP and TEP, the expression of dopaminergic-specific genes (LMX1B, FOXA2, EN1, and NURR1), and the secretion level of dopamine were significantly improved up to 3.3-fold and 3.0-fold, respectively, while the expression of Alzheimer genes (PSEN1, PSEN2, and APP), and the secretion of amyloid precursor protein were significantly reduced by 32-fold and 108-fold, respectively. Importantly, the autophagy activity was upregulated by CMP and TEP at 6.3- and 5.5-fold changes, respectively. Conclusions: This finding suggested that the nanoencapsulated cordyceps and turmeric extracts accelerated neuronal maturation and alleviated neuronal pathology in human neural cells. This paves the way for nanotechnology-driven drug delivery systems that could potentially be used as an alternative medicine in the future for neurological diseases. © 2022, The Author(s) under exclusive licence to Biomedical Engineering Society. Keyword: Autophagy; Cordyceps; Nanoencapsulation; Neuronal maturation; Turmeric Scopus Link: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85143895477&doi=10.1007%2fs12195-022-00752-w&partnerID=40&md5=cb694feca3831334eb9d8b56fd26a19b DOI: 10.1007/s12195-022-00752-w
2023		Nanoencapsulated cordyceps extract enhances collagen synthesis and skin cell regeneration through antioxidation and autophagy Upatcha N., Kaokaen P., Sorraksa N., Phonchai R., Kunhorm P., Chaicharoenaudomrung N., Noisa P.	Journal of Microencapsulation
Abstract: Oxidative stress from reactive oxygen species is the main cause of skin ageing. Cordycepin, a bioactive compound of Cordyceps militaris, contains antioxidant activity. This study examined extracellular matrix, antioxidant effect, autophagy activity, and skin regeneration in human dermal fibroblasts (HDFs) under normal and oxidative stress conditions. Slow disintegration was used to create nano-encapsulated cordyceps extract. HDFs were cultured and treated with 1 M cordycepin, 1 M medium, 0.1 M cordyceps medium loaded nanoparticles (CMP), or 1 mM H2O2. HDFs’ senescent phenotypes were assessed, including cell proliferation, ROS scavenging, collagen and elastin synthesis, antioxidant activity, and wound healing. CMP size averaged 184.5 ± 95.2 nm increased cell proliferation and reduced H2O2-induced ROS. Thus, HDFs treated for 48 h increased skin regeneration activity 2.76-fold by expressing extracellular matrix and rescuing H2O2-induced damaged cells. It was significant that this CMP inhibited H2O2-induced oxidative stress and induced autophagy to regenerate HDFs. The developed CMP could be used in cosmetics. © 2023 Informa UK Limited, trading as Taylor & Francis Group. Keyword: antioxidation; autophagy; cordyceps extract; Nanoencapsulation; skin regeneration Scopus Link: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85152389269&doi=10.1080%2f02652048.2023.2198008&partnerID=40&md5=50d55a8a6c2bb76066784bd04f821e6a DOI: 10.1080/02652048.2023.2198008
2023		Hispolon, A Bioactive Compound from Phellinus linteus, Induces Apoptosis of Human Breast Cancer Cells Through the Modulation of Oxidative Stress and Autophagy Pangjantuk A., Chueaphromsri P., Kunhorm P., Phonchai R., Chumkiew S., Chaicharoenau-domrung N., Noisa P.	Journal of Biologically Active Products from Nature
Abstract: Breast cancer (BC) is a major type of cancer found in women worldwide, accounting for more than 25% of all females diagnosed as BC patients. The BC treatment still needs to be highly effective with few adverse effects on the rest of the body. This study's objective was to investigate how hispolon enhanced anticancer activities and examine the underlying processes in human breast cancer cells. Hispolon was used to treat the HTB-26 cell lines. We investigated cell viability, intracellular reactive oxygen species (ROS) production, immunofluorescence straining, MDC assay, and RT-PCR. According to the findings, hispolon inhibited HTB-26 cells from proliferating and caused them to undergo apoptosis. When the mechanism of action of hispolon was investigated, it was discovered that BCL-2 expression was downregulated while pro-apoptotic genes including caspase-3, caspase-9, and BAX were upregulated. The level of intracellular ROS was also shown to be increased by hispolon, and the expression of antioxidant genes including SOD, GPX, and Catalase was found to be downregulated. The increase in the confocal fluorescence image of LC3I/II and the identification of upregulated autophagy-related genes, such as LC3I/II, ATG5, ATG10, and ATG12, served as indicators of the activation of autophagy. Therefore, our findings showed that hispolon had great potential for being an effective therapeutic agent and could cause cell death in breast cancer cells. © 2023 Har Krishan Bhalla & Sons. Keyword: Apoptosis; Autophagy; Breast cancer; Hispolon; Reactive oxygen species Scopus Link: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85152376344&doi=10.1080%2f22311866.2023.2191994&partnerID=40&md5=7d72448572cd7030e174cf27d8bfeab6 DOI: 10.1080/22311866.2023.2191994