Anthocyanins and Proanthocyanidins in Natural Pigmented Rice and Their Bioactivities

Natural pigmented rice is mainly black, red, and dark purple and contains a variety of flavones, tannins, phenolic, sterols, oryzanols, and essential oils. Anthocyanins and proanthocyanidins belonging to plant flavonoids are thought of as the major functional components found in black, red, and purple rice and contribute to the intense color of many fruits, vegetables, and pigmented cereals such as blueberries, grapes, red cabbages, and purple sweet potatoes. Recent data have indicated the potential for isolating and characterizing the nutrition and non-nutritive components in colored fruits, vegetables, and cereals for their potential chemopreventive and pharmaceutical agents. This chapter provides up-to-date coverage of pigmented rice in terms of the bioactive constituents, isolation, extraction and analytical methods, and related bioactivities. Special focus has been placed on the anti-inflammation, anticancer, and antiaging processes of the major components found in pigmented rice, especially with regard to germ and bran extracts

A pharmacological strategy using stemofoline for more efficacious chemotherapeutic treatments against human multidrug resistant leukemic cells

Our previous study reported that stemofoline (STF) exhibited a synergistic effect with chemotherapeutic drugs in human multidrug-resistant (MDR) leukemic cells (K526/Adr) by inhibiting the function of P-glycoprotein, which is a membrane transporter that is overexpressed in several types of MDR cancers. This study further investigated the effects of a combination treatment of STF and doxorubicin (DOX) in vitro and in vivo. The combination treatment of 50 mg/kg of STF strongly enhanced the anti-tumor activity of DOX in SCID-beige mice bearing K562/Adr xenografts without additional toxicity when compared to the single treatment groups. Additionally, an examination of the proliferation markers (Ki67) and the apoptotic marker (TUNEL) in tumor tissues in each group revealed that the combination therapy significantly reduced Ki67 positive cells and increased apoptotic cells. From the in vitro experiments we also found that this combination treatment dramatically induced G1 and G2M arrest in K562/Adr when compared to a single treatment of DOX. STF treatment alone did not show any cytotoxic effect to the cells. These results suggest that the accumulation of DOX enhanced by STF was sufficient to induce cell cycle arrest in K562/Adr. These findings support our previous in vitro data and indicate the possibility of developing STF as an adjuvant therapy in cancer treatments

Pyrogallol from <i>Spirogyra neglecta</i> Inhibits Proliferation and Promotes Apoptosis in Castration-Resistant Prostate Cancer Cells via Modulating Akt/GSK-3<i>β</i>/<i>β</i>-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 p p β in CRPC cell lines. Therefore, the phosphorylation of β-catenin was increased, which caused degradation of the protein, resulting in a downregulation of β-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

Photoprotective Effects of a Hyperoside-Enriched Fraction Prepared from <i>Houttuynia cordata</i> 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

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-&kappa;B 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-&alpha;-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

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&ndash;100 &mu;g/mL exhibited anti-inflammation activity for both A549 and THP-1 cells through the significant suppression of NLRP3, IL-1&beta;, and IL-18 inflammatory gene expressions and IL-6, IL-1&beta;, and IL-18 cytokine secretions in a dose-dependent manner (p &lt; 0.05). It was determined that both cell lines, C3G and P3G (at 1.25&ndash;10 &mu;g/mL), were compatibly responsible for the significant inhibition of SP-induced inflammatory responses for both gene and protein levels (p &lt; 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

Hesperetin from Root Extract of <i>Clerodendrum petasites</i> 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 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-1β, and IL-18 cytokine releases in A549 cells culture supernatant (p NLRP3, IL-1β, and IL-18, p C. petasites and hesperetin in the development of supportive therapies for the prevention of COVID-19-related chronic inflammation

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

Modulation of P-glycoprotein by Stemona alkaloids in human multidrug resistance leukemic cells and structural relationships

Background: Multidrug resistance (MDR) is a major reason for the failure of chemotherapy in the treatment of cancer patients. P-gp over-expression in MDR cancer cells is a multifactorial phenomenon with biochemical resistance mechanisms. Stemofoline (STF), isolated from Stemona bukillii, has been reported to be an MDR reversing compound. Purpose: This study investigated whether other Stemona alkaloids that had been purified from Stemonaceae plants exerted MDR modulation activity. Methods: MTT assay was performed to determine the MDR reversing property of the alkaloids. Modulation of P-gp function by these compounds was investigated using cell cycle analysis and P-gp fluorescent substrate accumulation assays. P-gp expression was determined by Western blot analysis. We preliminarily examined the safety of these compounds in normal human fibroblasts and human peripheral blood mononuclear cells (PBMCs) using the MTT assay, and in red blood cells (human and rat) through in vitro hemolysis assays. Results: Three of the eight alkaloids tested, isostemofoline (ISTF), 11Z -didehydrostemofoline (11Z-DSTF) and 11E-didehydrostemofoline (11E-DSTF), enhanced the chemotherapeutic sensitivity of MDR leukemic K562/Adr cells, which overexpressed P-gp. The P-gp functional studies showed that these three alkaloids increased the accumulation of P-gp substrates, calcein-AM (C-AM) and rhodamine123 (Rho 123) in K562/Adr cells, while this effect was not seen in drug sensitive parental K562 cells. Whereas, the alkaloids did not alter P-gp expression as was determined by Western blotting analysis. Conclusion: The alkaloids reversed MDR via the inhibition of P-gp function. For pharmaceutical safety testing, the alkaloids were found to be not toxic to normal human fibroblasts and PBMCs. Moreover, the effective compounds did not induce hemolysis in either human or rat erythrocytes. These compounds may be introduced as potential candidate molecules for treating cancers exhibiting P-gp-mediated MDR

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