Exploring the Anticancer Potential of Traditional Thai Medicinal Plants: A Focus on Dracaena loureiri and Its Effects on Non-Small-Cell Lung Cancer.

Non-small-cell lung cancer (NSCLC) is renowned for its aggressive and highly metastatic nature. In recent years, there has been a surge in interest regarding the therapeutic potential of traditional medicinal plants. Dracaena loureirin (D. loureirin), Ficus racemosa Linn. (F. racemosa), and Harrisonia perforata (Blanco) Merr. (H. perforata) are prominent traditional medicinal herbs in Thailand, recognized for their diverse biological activities, including antipyretic and anti-inflammatory effects. However, their prospective anti-cancer properties against NSCLC remain largely unexplored. This study aimed to evaluate the anti-cancer attributes of ethanolic extracts obtained from D. loureiri (DLEE), F. racemosa (FREE), and H. perforata (HPEE) against the A549 lung adenocarcinoma cell lines. Sulforhodamine B (SRB) assay results revealed that only DLEE exhibited cytotoxic effects on A549 cells, whereas FREE and HPEE showed no such cytotoxicity. To elucidate the anti-cancer mechanisms of DLEE, cell cycle and apoptosis assays were performed. The findings demonstrated that DLEE inhibited cell proliferation and induced cell cycle arrest at the G0/G1 phase in A549 cells through the downregulation of key cell cycle regulator proteins, including cyclin D1, CDK-2, and CDK-4. Furthermore, DLEE treatment facilitated apoptosis in A549 cells by suppressing anti-apoptotic proteins (Bcl-2, Bcl-xl, and survivin) and enhancing apoptotic proteins (cleaved-caspase-3 and cleaved-PARP-1). In summary, our study provides novel insights into the significant anti-cancer properties of DLEE against A549 cells. This work represents the first report suggesting that DLEE has the capability to impede the growth of A549 lung adenocarcinoma cells through the induction of apoptosis.

Notopterol Suppresses IL-17-Induced Proliferation and Invasion of A549 Lung Adenocarcinoma Cells via Modulation of STAT3, NF-κB, and AP-1 Activation.

Interleukine-17 is a proinflammatory cytokine that promotes lung cancer growth and progression though the activation of the STAT3, NF-κB, and AP-1 signaling pathways. Therefore, blocking the IL-17-induced oncogenic pathway is a new strategy for the treatment of lung cancer. Notopterol, a furanocoumarin, has demonstrated anti-tumor effects in several types of tumors. However, its molecular function in relation to the IL-17-induced proliferation and invasion of A549 lung adenocarcinoma cells remains unknown. Here, notopterol exhibited an inhibitory effect on IL-17-promoted A549 cell proliferation and induced G0/G1 cell cycle arrest. Western blot analysis revealed that notopterol inhibited the expression of cell-cycle-regulatory proteins, including cyclin D1, cyclin E, CDK4, and E2F. Moreover, notopterol blocked IL-17-induced A549 cell migration and invasion by regulating the epithelial-mesenchymal transition (EMT) and reducing the expression of extracellular degradation enzymes. At the molecular level, notopterol treatment significantly down-regulated the IL-17-activated phosphorylation of Akt, JNK, ERK1/2, and STAT3, leading to a reduced level of transcriptional activity of NF-κB and AP-1. Collectively, our results suggest that notopterol blocks IL-17-induced A549 cell proliferation and invasion through the suppression of the MAPK, Akt, STAT3, AP-1, and NF-κB signaling pathways, as well as modulating EMT.

Protective Effects of Proanthocyanidin-Rich Fraction from Red Rice Germ and Bran on Lung Cell Inflammation via Inhibition of NF-κB/NLRP3 Inflammasome Pathway.

The activation of the NLRP3 inflammasome pathway during infectious pathogen-induced immunopathology can lead to chronic inflammation and various adverse health outcomes. Identification of functional foods with anti-inflammatory properties is crucial for preventing inflammation triggered by NLRP3 inflammasome activation. This study aimed to investigate the anti-inflammatory properties of a proanthocyanidin-rich fraction obtained from red rice germ and bran against lipopolysaccharide (LPS) and adenosine triphosphate (ATP)-induced condition in A549 lung cells. The proanthocyanidin-rich fraction from Yamuechaebia 3 red rice extract (YM3-PRF) was obtained using column chromatography with Sephadex LH20, and its total proanthocyanidin content was determined to be 351.43 ± 1.18 mg/g extract using the vanillin assay. A549 lung cells were pretreated with YM3-PRF at concentrations of 5-20 µg/mL prior to exposure to LPS (1 µg/mL) and ATP (5 nM). The results showed that YM3-PRF significantly inhibited the expression of inflammatory mRNAs (NLRP3, IL-6, IL-1ß, and IL-18) and the secretion of cytokines (IL-6, IL-1ß, and IL-18) in a dose-dependent manner (p < 0.05). Mechanistically, YM3-PRF exerted its anti-inflammatory effects by inhibiting NF-κB translocation and downregulating proteins associated with the NLRP3 inflammasome pathway (NLRP3, ASC, pro-caspase-1, and cleaved-caspase-1). These findings suggest that the proanthocyanidin-rich fraction from red rice germ and bran has protective effects and may serve as a potential therapeutic option for chronic inflammatory diseases associated with NLRP3 inflammasome activation.

Pyrogallol from Spirogyra neglecta Inhibits Proliferation and Promotes Apoptosis in Castration-Resistant Prostate Cancer Cells via Modulating Akt/GSK-3ß/ß-catenin Signaling Pathway.

Castration-resistant prostate cancer (CRPC) is an advanced form of prostate cancer associated with poor survival rates. The high proliferation and metastasis rates have made CRPC one of the most challenging types of cancer for medical practitioners and researchers. In this study, the anti-cancer properties and inhibition of CRPC progression by S. neglecta extract and its active constituents were determined using two CRPC cell lines, DU145 and PC3. The ethyl acetate fraction of S. neglecta (SnEA) was obtained using a solvent-partitioned extraction technique. The active constituents of SnEA were then determined using the HPLC technique, which showed that SnEA mainly contained syringic acid, pyrogallol, and p-coumaric acid phenolic compounds. After the determination of cytotoxic properties using the SRB assay, it was found that pyrogallol, but not the other two major compounds of SnEA, displayed promising anti-cancer properties in both CRPC cell lines. SnEA and pyrogallol were then further investigated for their anti-proliferation and apoptotic induction properties using propidium iodide and Annexin V staining. The results showed that SnEA and pyrogallol inhibited both DU145 and PC3 cell proliferation by inducing cell cycle arrest in the G0/G1 phase and significantly decreased the expression of cell cycle regulator proteins (cyclin D1, cyclin E1, CDK-2, and CDK-4, p < 0.001). SnEA and pyrogallol treatments also promoted apoptosis in both types of CRPC cells through significantly downregulating anti-apoptotic proteins (survivin, Bcl-2, and Bcl-xl, p < 0.001) and upregulating apoptotic proteins (cleaved-caspase-9, cleaved-caspase-3 and cleaved-PARP-1, p < 0.001). Mechanistic study demonstrated that SnEA and pyrogallol inactivated the Akt signaling pathway leading to enhancement of the active form of GSK-3ß in CRPC cell lines. Therefore, the phosphorylation of ß-catenin was increased, which caused degradation of the protein, resulting in a downregulation of ß-catenin (unphosphorylated form) transcriptional factor activity. The current results reflect the potential impact of S. neglecta extract and pyrogallol on the management of castration-resistant prostate cancer.

Diclofenac Sensitizes Signet Ring Cell Gastric Carcinoma Cells to Cisplatin by Activating Autophagy and Inhibition of Survival Signal Pathways.

Gastric cancer has one of the highest incidence rates of cancer worldwide while also contributing to increased drug resistance among patients in clinical practice. Herein, we have investigated the role of diclofenac (DCF) on sensitizing cisplatin resistance in signet ring cell gastric carcinoma cells (SRCGC). Non-toxic concentrations of DCF significantly augmented cisplatin-induced cell death in cisplatin-resistant SRCGC cells (KATO/DDP) but not in cisplatin-sensitive SRCGC cells (KATOIII). Consistently, concomitant treatment of DCF and cisplatin significantly enhanced autophagic cell death due to overproduction of intracellular reactive oxygen species (ROS). At the molecular level, the induction of ROS has been associated with a reduction in antioxidant enzymes expression while inhibiting nuclear factor erythroid 2-related factor 2 (Nrf2) activity. Moreover, the combination of DCF and cisplatin also inhibited the expression of survival proteins including Bcl-2, Bcl-xL, cIAP1 and cyclin D1 in KATO/DDP cells when compared with cisplatin alone. This was due, at least in part, to reduce MAPKs, Akt, NF-κB, AP-1 and STAT-3 activation. Taken together, our results suggested that DCF potentiated the anticancer effect of cisplatin in SRCGC via the regeneration of intracellular ROS, which in turn promoted cell death as an autophagy mechanism and potentially modulated the cell survival signal transduction pathway.

Hesperetin from Root Extract of Clerodendrum petasites S. Moore Inhibits SARS-CoV-2 Spike Protein S1 Subunit-Induced NLRP3 Inflammasome in A549 Lung Cells via Modulation of the Akt/MAPK/AP-1 Pathway.

Inhibition of inflammatory responses from the spike glycoprotein of SARS-CoV-2 (Spike) by targeting NLRP3 inflammasome has recently been developed as an alternative form of supportive therapy besides the traditional anti-viral approaches. Clerodendrum petasites S. Moore (C. petasites) is a Thai traditional medicinal plant possessing antipyretic and anti-inflammatory activities. In this study, C. petasites ethanolic root extract (CpEE) underwent solvent-partitioned extraction to obtain the ethyl acetate fraction of C. petasites (CpEA). Subsequently, C. petasites extracts were determined for the flavonoid contents and anti-inflammatory properties against spike induction in the A549 lung cells. According to the HPLC results, CpEA significantly contained higher amounts of hesperidin and hesperetin flavonoids than CpEE (p < 0.05). A549 cells were then pre-treated with either C. petasites extracts or its active flavonoids and were primed with 100 ng/mL of spike S1 subunit (Spike S1) and determined for the anti-inflammatory properties. The results indicate that CpEA (compared with CpEE) and hesperetin (compared with hesperidin) exhibited greater anti-inflammatory properties upon Spike S1 induction through a significant reduction in IL-6, IL-1ß, and IL-18 cytokine releases in A549 cells culture supernatant (p < 0.05). Additionally, CpEA and hesperetin significantly inhibited the Spike S1-induced inflammatory gene expressions (NLRP3, IL-1ß, and IL-18, p < 0.05). Mechanistically, CpEA and hesperetin attenuated inflammasome machinery protein expressions (NLRP3, ASC, and Caspase-1), as well as inactivated the Akt/MAPK/AP-1 pathway. Overall, our findings could provide scientific-based evidence to support the use of C. petasites and hesperetin in the development of supportive therapies for the prevention of COVID-19-related chronic inflammation.

Cyanidin-3-O-glucoside and Peonidin-3-O-glucoside-Rich Fraction of Black Rice Germ and Bran Suppresses Inflammatory Responses from SARS-CoV-2 Spike Glycoprotein S1-Induction In Vitro in A549 Lung Cells and THP-1 Macrophages via Inhibition of the NLRP3 Inflammasome Pathway.

Black rice is a functional food that is high in anthocyanin content, primarily C3G and P3G. It possesses nutraceutical properties that exhibit a range of beneficial effects on human health. Currently, the spike glycoprotein S1 subunit of SARS-CoV-2 (SP) has been reported for its contribution to pathological inflammatory responses in targeting lung tissue and innate immune cells during COVID-19 infection and in the long-COVID phenomenon. Our objectives focused on the health benefits of the C3G and P3G-rich fraction of black rice germ and bran (BR extract) on the inhibition of inflammatory responses induced by SP, as well as the inhibition of NF-kB activation and the NLRP3 inflammasome pathway in an in vitro model. In this study, BR extract was identified for its active anthocyanins, C3G and P3G, using the HPLC technique. A549-lung cells and differentiated THP-1 macrophages were treated with BR extract, C3G, or P3G prior to exposure to 100 ng/mL of SP. Their anti-inflammatory properties were then determined. BR extract at concentrations of 12.5−100 µg/mL exhibited anti-inflammation activity for both A549 and THP-1 cells through the significant suppression of NLRP3, IL-1ß, and IL-18 inflammatory gene expressions and IL-6, IL-1ß, and IL-18 cytokine secretions in a dose-dependent manner (p < 0.05). It was determined that both cell lines, C3G and P3G (at 1.25−10 µg/mL), were compatibly responsible for the significant inhibition of SP-induced inflammatory responses for both gene and protein levels (p < 0.05). With regard to the anti-inflammation mechanism, BR extract, C3G, and P3G could attenuate SP-induced inflammation via counteraction with NF-kB activation and downregulation of the inflammasome-dependent inflammatory pathway proteins (NLRP3, ASC, and capase-1). Overall, the protective effects of anthocyanins obtained from black rice germ and bran can be employed in potentially preventive strategies that use pigmented rice against the long-term sequelae of COVID-19 infection.

Collagen Deposition and Inflammatory Response Associated with Macroporous Mesh Shrinkage in Incisional Hernia Repair: A Rat Model.

Background: Mesh repair is the current recommendation for the treatment of incisional hernia; however, the best mesh has yet to be determined. The objective of this study was to compare the inflammatory response and collagen deposition in primary incisional hernia repair (P) and different macroporous mesh materials, including polypropylene with poliglecaprone (PP-PG), polyvinylidene fluoride (PVDF), and polyester (PE), using quantitative methods. Methods: Sixty male rats were divided into four groups. Anterior abdominal wall defects were created and either suture or mesh repair was done. Rats were euthanized on days 14, 90, and 180, and the gross findings were recorded. The inflammatory and collagen levels in the abdominal wall tissues were measured using enzyme-linked immunosorbent assay (ELISA). Results: The PE group demonstrated significant mesh shrinkage at 180 days. The extent of PE mesh shrinkage ranged from 22-42% (mean = 30.49%). At 14 days, the PVDF group had higher interleukin-6 (IL-6) levels than the PP-PG (P = .004) and PE groups (P = .019). At 90 days, the collagen type I (Col I) levels in the PE group were significantly lower than those in the others, and the collagen type I/III (Col I/III) ratios in the PE group were lower than those in the P group (P = .006). Conclusions: The persistently high IL-6 levels until 180 days and the decrease in Col I levels and Col I/III ratio at 90 days seem to predict mesh shrinkage at 180 days. The mesh induces high Col I levels, but those associated with low Col III levels should be preferred.

Hyperoside and Quercitrin in Houttuynia cordata Extract Attenuate UVB-Induced Human Keratinocyte Cell Damage and Oxidative Stress via Modulation of MAPKs and Akt Signaling Pathway.

Ultraviolet radiation is a major environmental harmful factor on human skin. In this paper, we investigate the potential mechanism of Houttuynia cordata extract on UVB-induced HaCaT keratinocyte cell death and inflammation. We found that Houttuynia cordata ethyl acetate extract fraction (HC-EA) protected against UVB-induced cell damage. The HPLC results indicate that quercitrin and hyperoside are the major polyphenolics in HC-EA and are responsible for providing protection against UVB-induced cell death. These responses were associated with the regulation of caspase-9 and caspase-3 activation, which rescued HaCaT cells from UVB-induced apoptosis. In addition, HC-EA, quercitrin, and hyperoside attenuated UVB-induced inflammatory mediators, including IL-6, IL-8, COX-2, and iNOS. Furthermore, the treatment of cells with HC-EA and its active compounds abolished intracellular ROS and increased levels of heme oxygenase-1 and superoxide dismutase. UVB-induced ROS production mediated Akt and mitogen activated protein kinases (MAPKs) pathways, including p38, ERK, and JNK. Our results show HC-EA, quercitrin, and hyperoside decreased UVB-induced p38 and JNK phosphorylation, while increasing ERK and Akt phosphorylation. MAPKs and Akt mediated cell survival and death were confirmed by specific inhibitors to Akt and MAPKs. Thus, HC-EA, which contains quercitrin and hyperoside, protected keratinocyte from UVB-induced oxidative damage and inflammation through the modulation of MAPKs and Akt signaling.

Anti-Osteoporosis Effect of Perilla frutescens Leaf Hexane Fraction through Regulating Osteoclast and Osteoblast Differentiation.

Osteoporosis is the result of an imbalance in the bone-remodeling process via an increase in osteoclastic activity and a decrease in osteoblastic activity. Our previous studies have shown that Perilla frutescens seed meal has anti-osteoclastogenic activity. However, the role of perilla leaf hexane fraction (PLH) in osteoporosis has not yet been investigated and reported. In this study, we aimed to investigate the effects of PLH in osteoclast differentiation and osteogenic potential using cell-based experiments in vitro. From HPLC analysis, we found that PLH contained high luteolin and baicalein. PLH was shown to inhibit RANKL-induced ROS production and tartrate-resistant acid phosphatase (TRAP)-positive multi-nucleated osteoclasts. Moreover, PLH significantly downregulated the RANKL-induced MAPK and NF-κB signaling pathways, leading to the attenuation of NFATc1 and MMP-9 expression. In contrast, PLH enhanced osteoblast function by regulating alkaline phosphatase (ALP) and restoring TNF-α-suppressed osteoblast proliferation and osteogenic potential. Thus, luteolin and baicalein-rich PLH inhibits osteoclast differentiation but promotes the function of osteoblasts. Collectively, our data provide new evidence that suggests that PLH may be a valuable anti-osteoporosis agent.

Photoprotective Effects of a Hyperoside-Enriched Fraction Prepared from Houttuynia cordata Thunb. on Ultraviolet B-Induced Skin Aging in Human Fibroblasts through the MAPK Signaling Pathway.

Ultraviolet-B (UVB) irradiation causes skin damage via deleterious effects including oxidative stress, inflammation, and collagen degradation. The photoprotective effects of a hyperoside-enriched fraction obtained from Houttuynia cordata Thunb. (H. cordata) on the attenuation of UVB-induced skin aging in human fibroblasts were investigated. The solvent-partition technique was used to establish the hyperoside-enriched fraction of H. cordata (HcEA). The active compounds identified in the H. cordata extracts were hyperoside, quercitrin, chlorogenic acid, and rutin. With regard to the photoprotective effects of H. cordata on UVB-irradiated dermal fibroblasts, HcEA and hyperoside inhibited intracellular ROS production and inflammatory cytokine secretions (IL-6 and IL-8), while increasing collagen type I synthesis along with downregulating MMP-1 gene and protein expressions. Mechanistically, the hyperoside-enriched fraction obtained from H. cordata inhibited UVB-irradiated skin aging through regulation of the MAPK signaling pathway by attenuating the activation of JNK/ERK/c-Jun in human dermal fibroblasts. The hyperoside-enriched fraction of H. cordata exerted potent anti-skin aging properties against UVB exposure. The findings of this study can be applied in the cosmetics industry, as H. cordata extract can potentially be used in pharmaceutical or cosmetic formulations as a photoprotective or anti-skin aging agent.

Transcriptomic Profiling Reveals AKR1C1 and AKR1C3 Mediate Cisplatin Resistance in Signet Ring Cell Gastric Carcinoma via Autophagic Cell Death.

Signet ring cell gastric carcinoma (SRCGC) is a lethal malignancy that has developed drug resistance to cisplatin therapies. The aim of this study was to characterize the acquisition of the cisplatin-resistance SRCGC cell line (KATO/DDP cells) and to understand the molecular mechanisms underlying cisplatin resistance. Transcriptomic and bioinformatic analyses were used to identify the candidate gene. This was confirmed by qPCR and Western blot. Aldoketoreductase1C1 and 1C3 (AKR1C1 and AKR1C3) were the most promising molecules in KATO/DDP cells. A specific inhibitor of AKR1C1 (5PBSA) and AKR1C3 (ASP9521) was used to enhance cisplatin-induced KATO/DPP cell death. Although cisplatin alone induced KATO/DDP apoptosis, a combination treatment of cisplatin and the AKR1C inhibitors had no influence on percent cell apoptosis. In conjunction with the autophagy inhibitor, 3MA, attenuated the effects of 5PBSA or ASP9521 to enhance cisplatin-induced cell death. These results indicated that AKR1C1 and 1C3 regulated cisplatin-induced KATO/DDP cell death via autophagy. Moreover, cisplatin in combination with AKR1C inhibitors and N-acetyl cysteine increased KATO/DDP cells' viability when compared with a combination treatment of cisplatin and the inhibitors. Taken together, our results suggested that AKR1C1 and 1C3 play a crucial role in cisplatin resistance of SRCGC by regulating redox-dependent autophagy.

Suppressive Effects of Rosmarinic Acid Rich Fraction from Perilla on Oxidative Stress, Inflammation and Metastasis Ability in A549 Cells Exposed to PM via C-Jun, P-65-Nf-Κb and Akt Signaling Pathways.

Particulate matter from forest fires (PMFF) is an environmental pollutant causing oxidative stress, inflammation, and cancer cell metastasis due to the presence of polycyclic aromatic hydrocarbons (PAHs). Perilla seed meal contains high levels of polyphenols, including rosmarinic acid (RA). The aim of this study is to determine the anti-oxidative stress, anti-inflammation, and anti-metastasis actions of rosmarinic acid rich fraction (RA-RF) from perilla seed meal and its underlying molecular mechanisms in A549 cells exposed to PMFF. PMFF samples were collected via the air sampler at the University of Phayao, Thailand, and their PAH content were analyzed using GC-MS. Fifteen PAH compounds were detected in PMFF. The PMFF significantly induced intracellular reactive oxygen species (ROS) production, the mRNA expression of pro-inflammatory cytokines, MMP-9 activity, invasion, migration, the overexpression of c-Jun and p-65-NF-κB, and Akt phosphorylation. Additionally, the RA-RF significantly reduced ROS production, IL-6, IL-8, TNF-α, and COX-2. RA-RF could also suppress MMP-9 activity, migration, invasion, and the phosphorylation activity of c-Jun, p-65-NF-κB, and Akt. Our findings revealed that RA-RF has antioxidant, anti-inflammatory, and anti-metastasis properties via c-Jun, p-65-NF-κB, and Akt signaling pathways. RA-RF may be further developed as an inhalation agent for the prevention of lung inflammation and cancer metastasis induced by PM exposure.

Determination of Phenolic Content, Antioxidant Activity, and Tyrosinase Inhibitory Effects of Functional Cosmetic Creams Available on the Thailand Market.

Recently, the global trend toward the use of natural extracts and antioxidant agents in the cosmetic cream industry to produce whitening effects has been increasing. This has also been a persistent trend in Thailand. In this study, samples of commercial cosmetic creams on the Thai market were assessed for a functional evaluation of their antioxidant activity, tyrosinase inhibitory effects, and phenolic contents. Samples were extracted using hot water and sonication extraction method to obtain the functional cream extracts. Total phenolic contents in all samples were within the range of 0.46-47.92 mg GAE/30 g cream. Antioxidant activities of the cream extracts were within the range of 3.61-43.98 mg Trolox equivalent/30 g cream, while tyrosinase inhibition activities were within the range of 2.58-97.94% of inhibition. With regard to the relationship between the total phenolic content and the antioxidant activity of the cosmetic creams, Pearson's correlation coefficient revealed a moderately positive relationship with an r value of 0.6108. Furthermore, the relationship between the antioxidant activity and the tyrosinase inhibitory activity of the cosmetic creams was highly positive with an r value of 0.7238. Overall, this study demonstrated that the total phenolic contents in the functional cosmetic creams could play a role in antioxidant activity and anti-tyrosinase activities. The findings indicate how the whitening and antioxidant effects of cosmetic creams could be maintained after the products have been formulated, as this concern can affect the consumer's decision when purchasing cosmetic products.

Skin Wound-Healing Potential of Polysaccharides from Medicinal Mushroom Auricularia auricula-judae (Bull.).

Auricularia auricula-judae, a nutrient-rich mushroom used in traditional medicine, is a macrofungi that exhibits various biological properties. In this study, we have reported on the mechanisms that promote the wound-healing effects of a water-soluble polysaccharide-rich extract obtained from A. auricula-judae (AAP). AAP contained high amounts of polysaccharides (349.83 ± 5.00 mg/g extract) with a molecular weight of 158 kDa. The main sugar composition of AAP includes mannose, galactose, and glucose. AAP displayed antioxidant activity in vitro and was able to abort UVB-induced intracellular ROS production in human fibroblasts in cellulo. AAP significantly promoted both fibroblast and keratinocyte proliferation, migration, and invasion, along with augmentation of the wound-healing process by increasing collagen synthesis and decreasing E-cadherin expression (All p < 0.05). Specifically, the AAP significantly accelerated the wound closure in a mice skin wound-healing model on day 9 (2.5%AAP, p = 0.031 vs. control) and day 12 (1% and 2.5%AAP with p = 0.009 and p < 0.001 vs. control, respectively). Overall, our results indicate that the wound-healing activities of AAP can be applied in an AAP-based product for wound management.

Antifungal Activity and Molecular Mechanisms of Partial Purified Antifungal Proteins from Rhinacanthus nasutus against Talaromyces marneffei.

Antifungal proteins (AFPs) are able to inhibit a wide spectrum of fungi without significant toxicity to the hosts. This study examined the antifungal activity of AFPs isolated from a Thai medicinal plant, Rhinacanthus nasutus, against the human pathogenic fungus Talaromycesmarneffei. This dimorphic fungus causes systemic infections in immunocompromised individuals and is endemic in Southeast Asian countries. The R. nasutus crude protein extract inhibited the growth of T. marneffei. The anti-T. marneffei activity was completely lost when treated with proteinase K and pepsin, indicating that the antifungal activity was dependent on a protein component. The total protein extract from R. nasutus was partially purified by size fractionation to ≤10, 10-30, and ≥30 kDa fractions and tested for the minimal inhibitory concentration (MIC) and minimal fungicidal concentration (MFC). All fractions showed anti-T. marneffei activity with the MIC and MFC values of 32 to 128 µg/mL and >128 µg/mL, respectively. In order to determine the mechanism of inhibition, all fractions were tested with T. marneffei mutant strains affected in G-protein signaling and cell wall integrity pathways. The anti-T. marneffei activity of the 10-30 kDa fraction was abrogated by deletion of gasA and gasC, the genes encoding alpha subunits of heterotrimeric G-proteins, indicating that the inhibitory effect is related to intracellular signaling through G-proteins. The work demonstrates that antifungal proteins isolated from R. nasutus represent sources for novel drug development.

Dehydrozingerone, a Curcumin Analog, as a Potential Anti-Prostate Cancer Inhibitor In Vitro and In Vivo.

Curcumin (Cur) exhibits biological activities that support its candidacy for cancer treatment. However, there are limitations to its pharmacological effects, such as poor solubility and bioavailability. Notably, the use of Cur analogs has potential for addressing these limitations. Dehydrozingerone (DZG) is a representative of the half-chemical structure of Cur, and many reports have indicated that it is anticancer in vitro. We, therefore, have hypothesized that DZG could inhibit prostate cancer progression both in vitro and in vivo. Results revealed that DZG decreased cell proliferation of rat castration-resistant prostate cancer, PLS10 cells, via induction of the cell cycle arrest in the G1 phase in vitro. In the PLS10 xenograft model, DZG significantly decreased the growth of subcutaneous tumors when compared to the control via the inhibition of cell proliferation and angiogenesis. To prove that DZG could improve the limitations of Cur, an in vivo pharmacokinetic was determined. DZG was detected in the serum at higher concentrations and remained up to 3 h after intraperitoneal injections, which was longer than Cur. DZG also showed superior in vivo tissue distribution than Cur. The results suggest that DZG could be a candidate of the Cur analog that can potentially exert anticancer capabilities in vivo and thereby improve its bioavailability.

Multicomponent Exercise Program Reduces Frailty and Inflammatory Biomarkers and Improves Physical Performance in Community-Dwelling Older Adults: A Randomized Controlled Trial.

The efficacy of exercise to reverse frailty in the aging population has not been extensively investigated. This study aimed to investigate the effectiveness of a multicomponent exercise program (MCEP) on frailty, physical performance (handgrip strength, Berg Balance Scale (BBS), Timed Up and Go test (TUG), and VO2Max), blood biomarkers (Interleukin-6 (IL-6) and C-reactive protein (CRP)) in frail older adults. A randomized controlled trial using an allocation concealment method, included 64 older adults (77.78 ± 7.24 years), were divided into two parallel groups using block randomization: an MCEP group (n = 32) and a control group (n = 32). The combined center- and home-based MCEP training consisted of chair aerobic, resistance, and balance, which was carried out 3 days per week for 24 weeks. A mixed model repeated measure ANOVA demonstrated significant interaction effects of group x time for BBS, TUG and frailty scores (p < 0.001). Additionally, the post-hoc analysis revealed that the MCEP group showed significantly improved BBS, TUG, and frailty scores (p < 0.01), at both 12- and 24-weeks. When compared with controls at 12-weeks, the MCEP group decreased IL-6 and CRP levels (p < 0.05). The combined center- and home-based MCEP were effective in reversing frailty to pre-frailty and improving physical performance especially balance in the older population.

Combined Black Rice Germ, Bran Supplement and Exercise Intervention Modulate Aging Biomarkers and Improve Physical Performance and Lower-Body Muscle Strength Parameters in Aging Population.

Aging is a time-dependent functional decline in muscle mass and strength, which is reflected in poor physical performances, hormonal imbalance, and development of chronic low-grade inflammation. This study aimed to assess the effectiveness of black rice germ, bran supplement, and exercise program either alone or in combination for 24 weeks on the aging biomarkers (C-reactive protein, Interleukin-6, Insulin-like growth factor-1, and CD4:CD8 T cell ratio) physical performance, muscle strength parameters (walking speed, sit-to-stand time, grip strength) among Thai aging population. A total of 120 healthy volunteers aged 65-74 years were assigned to the exercise group (EX), black rice germ, and bran supplement (BR) group or the combination of BR and EX group (BR + EX). Over the course of the 24-week intervention, compared with baseline data (T0), the combined BR + EX intervention significantly decreased the inflammatory biomarkers (C-reactive protein and interleukin-6 levels, both p < 0.05 vs. T0) and significantly increased the insulin-like growth factor-1 levels (p < 0.001 vs. T0). Significant improvement in physical performance and muscle strength were also observed in the combined BR + EX group (decrease in sit-to-stand time and gait speed over the 24-week intervention, both p < 0.05 vs. T0, and trend toward grip strength improvement at p = 0.088 vs. T0). Overall, our results indicated a synergistic effect towards the combined intervention with the sustainable improvement in physical performances, lower-body muscle strength, and the modulation of both inflammatory and endocrine biomarkers. This study could encourage older adults to change their lifestyles to improve healthy aging and longevity.

Dicentrine Potentiates TNF-α-Induced Apoptosis and Suppresses Invasion of A549 Lung Adenocarcinoma Cells via Modulation of NF-κB and AP-1 Activation.

Numerous studies have indicated that tumor necrosis factor-alpha (TNF-α) could induce cancer cell survival and metastasis via activation of transcriptional activity of NF-κB and AP-1. Therefore, the inhibition of TNF-α-induced NF-κB and AP-1 activity has been considered in the search for drugs that could effectively treat cancer. Dicentrine, an aporphinic alkaloid, exerts anti-inflammatory and anticancer activities. Therefore, we investigated the effects of dicentrine on TNF-α-induced tumor progression in A549 lung adenocarcinoma cells. Our results demonstrated that dicentrine effectively sensitizes TNF-α-induced apoptosis in A549 cells when compared with dicentrine alone. In addition, dicentrine increases caspase-8, -9, -3, and poly (ADP-ribose) polymerase (PARP) activities by upregulating the death-inducing signaling complex and by inhibiting the expression of antiapoptotic proteins including cIAP2, cFLIP, and Bcl-XL. Furthermore, dicentrine inhibits the TNF-α-induced A549 cells invasion and migration. This inhibition is correlated with the suppression of invasive proteins in the presence of dicentrine. Moreover, dicentrine significantly blockes TNF-α-activated TAK1, p38, JNK, and Akt, leading to reduced levels of the transcriptional activity of NF-κB and AP-1. Taken together, our results suggest that dicentrine could enhance TNF-α-induced A549 cell death by inducing apoptosis and reducing cell invasion due to, at least in part, the suppression of TAK-1, MAPK, Akt, AP-1, and NF-κB signaling pathways.