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Background and Objective: Tomato seeds are edible seeds unconsciously ingested with the fruit. However, there are few reports regarding the constituents and biological activities of tomato seed extract (TSE). Recently, we found that saponins are major constituents of TSE including lycoperoside H. Previous reports have described that several plant-derived saponins improve skin diseases such as wounds and microangiopathy. Therefore, to discover the effect of TSE on the skin condition, we conducted a clinical trial of TSE (Tomato Seed Extract-P) standardized with lycoperoside H when orally ingested. Methods: The study was performed as a randomized, double-blind, placebo-controlled study. TSE (200 mg daily) containing 1 mg of lycoperoside H was used as the active sample. We enrolled 44 Japanese women who have concerns about facial elasticity and relatively low facial skin elasticity. All subjects were randomly allocated into either the active group (n = 22) or the placebo group (n = 22) using a computerized random-number generator. Capsules containing either the active sample or a placebo were administered for 8 weeks between October 12, 2020, and January 16, 2021. Facial elasticity, specifically the R7 value, was evaluated as the primary outcome. The remaining facial R parameters, upper arm R parameters, and other skin parameters including epidermal moisture, trans epidermal water loss, dermal parameters, and advanced glycation end products (AGEs) parameters were measured at 0, 4, and 8 weeks of ingestion. Blood, urine, and body parameters were also evaluated for safety. Results: Forty-three subjects completed the trial, and the per protocol set comprised 21 subjects in the TSE group and 22 subjects in the placebo group. After ingesting TSE for 8 weeks, the R7 value was significantly higher in the TSE group compared to the placebo group. Furthermore, the change in R7 values from the baseline at 4 and 8 weeks were also higher in the TSE group. Among the secondary outcomes, facial elasticity parameters including R2, R5, R1, and R4 at 4 weeks and facial R5, R1, and R4 and upper arm R2 at 8 weeks were higher in the TSE group. In addition, plasma pentosidine significantly decreased in the TSE group after 8 weeks of ingestion. There were no significant differences in moisture, DermaLab® parameters and AGEs parameters except plasma pentosidine. Laboratory tests revealed no abnormalities suggesting adverse effects of TSE. Conclusions: TSE (200 mg/day) standardized with lycoperoside H improved the facial elasticity parameters. Thus, daily ingestion of TSE was suggested to be beneficial for maintaining the facial skin elasticity. However, the relationship between the reduction of pentosidine and skin elasticity by TSE ingestion should be clarified through further studies. Trial Registration: UMIN-CTR: UMIN000041881. Foundation: Oryza Oil & Fat Chemical Co., Ltd.

Background and objective: The fruit of Mauritia flexuosa (moriche palm), which is known as “Aguaje,” has been used for beverages and processed foods. Recently, we found that several methoxyflavans are contained in the fruit and they exhibit estrogenic activities. Therefore, moriche palm extract (MPE) may function as a phytoestrogen and improve the symptoms induced by estrogen deficiency. However, the clinical effects of MPE on females has not yet been reported. We conducted a clinical trial of MPE on undefined complaints related to premenstrual syndrome (PMS) in healthy Japanese females. Methods: This randomized, double-blind, placebo-controlled study examined the effects of MPE (100 mg daily) containing 12.6  g of 5,4'-dihydroxy-7-methoxy-6-methylflavan. Forty-four Japanese women with indefinite complaints in premenstrual and menstrual periods were enrolled in the study. All subjects were randomly allocated into either the MPE (100 mg) group (n=22) or the placebo group (n=22) using a computerized random-number generator. Capsules containing either MPE (100 mg) or placebo were administered for 8 weeks between October and December in 2018. The severity of uncertain complaints and emotional status were evaluated using the Japanese version of the menstrual distress questionnaire (MDQ) as a primary outcome, and Medical Outcomes Study Short-Form 36-Item Health (SF-36) questionnaire at 4 and 8 weeks of ingestion. Blood, urine, and body parameters were also evaluated. Results: Forty-three subjects completed the trial, and the per protocol set comprised 21 subjects in the MPE (100 mg) group and 22 subjects in the placebo group. After ingesting MPE for 4 weeks, arousal in the premenstrual period significantly improved in the MPE (100 mg) group. After 8 weeks, the summary score, water retention, impaired concentration and control during menstrual period significantly improved in the MPE (100 mg) group. Contrarily, among SF-36 domain scores, significant ameliorating effects of MPE were not observed compared with those of the placebo group. Laboratory tests revealed no abnormalities suggesting adverse effects of MPE. Conclusions: MPE (100 mg/day for 8 weeks) improved several indefinite complaint parameters related to mensuration. MPE was suggested to be useful for improving anxiety related to PMS. Keywords: Menstrual distress questionnaire; SF-36 questionnaire; moriche palm; methoxyflavan; indefinite complaint

Background and objective: Chrysanthemum flowers are consumed as fresh condiments, herbal teas, and processed foods in Japan and Taiwan. They contain luteolin as a major polyphenol and are traditionally used for eye care. We previously demonstrated that the ingestion of Chrysanthemum flower extract (CFE) for 1 month reduced serum uric acid levels. However, the findings obtained were considered to be biased because the study was performed by a CFE manufacturer. Therefore, we herein conducted a clinical trial on CFE on a larger scale and examined its effects on purine base absorption from the intestines, which represents an effective approach for reducing serum uric acid levels. Methods: Both studies were performed as randomized, double-blind, placebo-controlled trials and CFE (100 mg) containing 1 mg of luteolin was used as the active sample. We enrolled 44 healthy Japanese men and women with 6.0 to 7.9 mg/dL serum uric acid. All subjects were randomly allocated to an active group (n=22) or placebo group (n=22) using a computerized random number generator. In the purine base absorption study, CFE was ingested with a purine base-rich diet and serum uric acid levels were measured chronologically. In the 12-week consecutive ingestion study, CFE or placebo was administered between January and April 2021. Serum uric acid levels after 12 weeks were assessed as the primary outcome, and uric acid were measured before and after 4 weeks of the intervention as secondary outcomes. Blood, urine and body parameters were examined to evaluate the safety of CFE. Results: Thirty-nine subjects completed the trial, and the per protocol set comprised 18 and 21 subjects in the active and placebo groups, respectively. In the single dosing study of CFE on subjects loaded by the purine base-rich diet, no significant changes were observed between the CFE and placebo groups. On the other hand, in the 12-week ingestion study, serum uric acid levels were significantly lower in the CFE group than in the placebo group. Laboratory tests revealed no abnormalities to suggest any side effects of CFE.Conclusions: CFE (100 mg/day) containing 1 mg of luteolin reduced serum uric acid levels. CFE may be beneficial for improving hyperurichemia. Trial Registration: UMIN-CTR: UMIN000042327Foundation: The present study was funded by Oryza Oil & Fat Chemical Co., Ltd. Keywords: Chrysanthemum, luteolin, uric acid, purine base

Background and objective: The ingestion of plant-derived glucosylceramides (GlcCer) has been reported to contribute to skin barrier function and hydration of the epidermis. b-sitosterol glucoside (BSG) colocalized with GlcCer in the rice hydrophobic fraction has been shown to increase ceramides in the stratum corneum in vitro . Although clinical studies demonstrated that GlcCer reduced transepidermal water loss (TEWL), the contribution of BSG to epidermal dehydration when applied with GlcCer remains unknown. Therefore, we herein conducted a clinical trial on the effects of a rice-derived mixed fraction of GlcCer and BSG (Oryza Ceramide ® ) on TEWL and other skin parameters. Methods: A randomized, double-blind, placebo-controlled study design was used. Oryza Ceramide ® (type PCD, 40 mg daily) containing 1.2 mg of GlcCer and 40 mg of BSG was used as the active sample. We enrolled 44 healthy Japanese women with epidermal dehydration. All subjects were randomly allocated to an active group (n=22) or placebo group (n=22) using a computerized random number generator. Capsules containing the active sample or placebo were administered for 12 weeks between August and December 2020. Cheek TEWL after 12 weeks was assessed as the primary outcome, and TEWL on a different part of the skin and various skin parameters, including epidermal moisture, pigmentation, pores, and elasticity, were measured before and after 4, 8, and 12 weeks of the intervention. Blood, urine, and body parameters were also examined to evaluate safety. Results: Forty-four subjects completed the trial, and the per protocol set comprised 22 each in the active and placebo groups. Cheek TEWL significantly reduced after the Oryza Ceramide ® intervention for 4 and 12 weeks. Among the secondary outcomes examined, lip moisture (12 weeks) and visible pore number (4 weeks) were improved by Oryza Ceramide ® . Laboratory tests revealed no abnormalities to suggest any adverse effects of Oryza Ceramide ® . Conclusions: Oryza Ceramide ® (40 mg/day) consisting of GlcCer and BSG improved facial TEWL, lip moisture, and visible pores, and these effects may be attributed to increases in epidermal ceramides. The combination of rice GlcCer and BSG appears to be beneficial for improving facial skin conditions. Trial Registration : UMIN-CTR: UMIN000041295 Foundation : The study was funded by Oryza Oil & Fat Chemical Co., Ltd. and Aichi Prefectural Subsidies for Research and Development of Creative Products in 2020. Keywords: rice; glucosylceramide; β -sitosterol glucoside; trans epidermal water loss; pore

Objective: To evaluate the effects of the eight-week consumption of Theracurmin® on liver function, fatigue, and sleep. Methods: This was a randomized, double-blind, placebo-controlled, parallel-comparison study involving 68 healthy Japanese adults. Subjects were allocated into either the active (Theracurmin®) or placebo group ( n = 34 each) using a random number generator. Subjects consumed two capsules per day of either the active or placebo food for eight weeks. The primary outcome was the serum alanine aminotransferase (ALT) levels at eight weeks, whereas the secondary outcomes were the biomarkers of liver function, comparison of the percentages of improvement in liver function based on the decision criteria, OSA sleep inventory MA version (OSA-MA), and visual analog scale of fatigue. Results: Each group included 33 subjects in the full analysis set. ALT levels in the per protocol set analysis, except for subjects drinking quantities of alcohol that increase the risk of lifestyle-related disease onset, showed a significant decrease in ALT compared to the placebo group ( P < 0.05). The subjective symptom in the fatigue recovery factor of OSA-MA was significantly improved through the intervention ( P < 0.05). The fatigue recovery effect of Theracurmin® was prominent in the subjects aged ≤ 45 years, the age group defined by the Ministry of Health, Labour and Welfare as middle-aged and older persons in the Act on Stabilization of Employment of Elderly. No adverse event was observed. Conclusions: These results suggest that the consumption of Theracurmin® or eight weeks improved liver function and fatigue recovery at awakening in healthy Japanese adults. Trial registration: UMIN-CTR: UMIN000039319. Foundation: Theravalues Corporation Keywords: highly bioavailable curcumin, liver function, alanine aminotransferase (ALT), OSA sleep inventory MA version, fatigue recovery

Background: To prevent diabetes, it is important to control postprandial glycemic levels. Studies have suggested that consuming black tea decreases the risk of type 2 diabetes; however, only a few studies have examined the effects of black tea on postprandial glycemic control after consuming starch-rich foods. In addition, the mechanism underlying the suppression of postprandial glucose levels remains unclear. Objective: To investigate the effects of black tea on postprandial blood glucose levels in healthy humans and to identify the components of black tea that inhibit digestive enzymes. Methods: The inhibitory activity of black tea on digestive enzymes was measured, and the inhibitory components were fractionated. Healthy Japanese adults ingested 200 ml of black tea, and its effect on postprandial blood glucose and insulin levels were investigated. Results: Black tea dose-dependently inhibited α-glucosidase, sucrase, and α-amylase activity. The major components responsible for this inhibition were high–molecular-weight polyphenols. The galloyl moieties present in these compounds play an important role in their inhibitory activities. Two randomized, double-blind, placebo-controlled, crossover studies of healthy human subjects (total n = 46) were conducted to investigate the effect of black tea on blood glucose and insulin levels. Combined data from the two studies showed that black tea ingestion (200 mL) after cooked rice intake (200 g) significantly reduced the incremental area under the curve of glucose ( P =.024) and insulin ( P =.014) compared to placebo drink. Conclusions: The high–molecular-weight polyphenols in black tea inhibited α-glucosidase, sucrase, and α-amylase activity in a dose-dependent manner. Furthermore, black tea ingestion after eating cooked rice significantly reduced the incremental area under the curve of glucose and insulin. These effects of black tea could be attributed to the inhibition of digestive enzymes by high–molecular-weight polyphenols containing galloyl groups. Keywords: black tea, blood glucose, α - glucosidase, α -amylase, polyphenol

Highlights • Excessive intake of B. subtilis C-3102 leads to unchanged in the medical condition. • Excessive intake of B. subtilis C-3102 does not worsen bone mineral density. • Excessive intake of B. subtilis C-3102 was safe under the study condition., Objective Continuous intake of Bacillus subtilis C-3102 (B. subtilis C-3102) has been reported to modulate the gut microbiota and increase the bone mineral density of the femur in healthy adults. This study aimed to evaluate the safety of excessive B. subtilis C-3102 intake through a randomized, placebo-controlled, double-blind, parallel-group study. Method A total of 69 individuals provided an informed consent, and 44 subjects who met the inclusion criteria were allocated to either the B. subtilis C-3102 (C-3102 group, n = 22) or the placebo group (P group, n = 22). All subjects took 18 tablets containing either containing B. subtilis C-3102 or placebo per day for 4 weeks with water and without chewing. Subjects in the C-3102 group consumed 4.8 × 1010 colony forming units (cfu) per day. Physical examination, urinalysis, blood analysis, records of subjective symptoms, and a medical questionnaire administered by a clinical trial physician were performed to determine the safety of test tablets. Furthermore, bone mineral density was measured. Results The final analysis included data from 22 subjects (9 men, 13 women; age, 46.1 ± 13.8 years) in the C-3102 group and 22 subjects (9 men, 13 women; age, 46.1 ± 13.5 years) in the P group. The results revealed no medical-related problems in both C-3102 and P groups. Conclusion This study proved the safety of 4-week continuous consumption of an excessive amount of B. subtilis C-3102 tablets.

This study aims to investigate the effects of MaquiBright®, also known as BrightSight®, a standardized maqui berry extract, on improving eye dryness and fatigue in Japanese subjects (aged 30–60 years) experiencing eye dryness, eye fatigue, and ≥4 h of visual display terminal (VDT) work daily. Seventy-four participants were equally but randomly assigned to either a MaquiBright® (MB) or a placebo (P) group, wherein each participant consumed one capsule daily for 4 weeks of the appropriate treatment (MaquiBright® 60 or 0 mg). Eye dryness and fatigue were measured using the Schirmer's test, tear break-up time (BUT) test, pupillary response, and flicker test before intake and 4 weeks after intake. Furthermore, subjective symptoms were assessed using the Visual Analogue Scale (VAS) method and the Dry Eye–related Quality of Life Score (DEQS) questionnaire. The MB group demonstrated a significantly higher lacrimal fluid production in both eyes (increased 6.4 ± 8.1 mm, P = 0.005) in Schirmer's test compared to the P group before VDT load (playing a video game) at 4 weeks after intake. In the VAS method after VDT load, the reduction of subjective symptoms in eye fatigue (P = 0.047) and stiff shoulders (P = 0.035) were significantly higher in the MB group than in the P group as well as bothersome ocular symptoms (P = 0.037) by the DEQS. No adverse events were reported. Thus, the consumption of 60 mg of MaquiBright® per day for 4 weeks reduced eye dryness and seemed to alleviate eye fatigue. Keywords: Maqui berry, Delphinidin, Schirmer's test, DEQS questionnaire, Lacrimal fluid production

Speradine A is a derivative of cyclopiazonic acid (CPA) found in culture of an Aspergillus tamarii isolate. Heterologous expression of a predicted methyltransferase gene, cpaM, in the cpa biosynthesis gene cluster of A. tamarii resulted in the speradine A production in a 2-oxoCPA producing A. oryzae strain, indicating cpaM is involved in the speradine A biosynthesis.