Beneficial effects of a nobiletin‐rich formulated supplement of Sikwasa (C. depressa) peel on cognitive function in elderly Japanese subjects; A multicenter, randomized, double‐blind, placebo‐controlled study

Abstract

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Perilla seed oil in combination with nobiletin-rich ponkan powder enhances cognitive function in healthy elderly Japanese individuals: a possible supplement for brain health in the elderly

“…Apart from anthocyanin, curcumin, and quercetin, nobiletin, an O -methylated flavonoid (methoxy flavonoid), isolated from citrus peels, has also been reported in a multicentre, randomized, double-blind, placebo-controlled study to have beneficial effects for improving memory dysfunction in healthy elderly subjects. 49 One clinical study found that nobiletin-rich citrus peel extract reduced cognitive impairment in Alzheimer's disease patients on donepezil therapy. 36 In numerous animal models of dementia, nobiletin has also been shown to ameliorate cognitive impairment by exhibiting neuroprotective effects against neuroinflammation and oxidative stress.…”

Tangeretin Inhibits BACE1 Activity and Attenuates Cognitive Impairments in AD Model Mice

“…LY2811376, a powerful BACE1-1 inhibitor, was used as the positive control drug in our study. We also compared TAN with nobiletin, another important polymethoxyflavone present in orange fruit peel. , Our calculations led to the prediction that Tan exhibited a high binding affinity for BACE1 (Figure ). Compared with LY2811376, TAN could be combined with BACE1 at a similar position.…”

Effectiveness and Safety of a Mixture of Nobiletin and Tangeretin in Nocturia Patients: A Randomized, Placebo-Controlled, Double-Blind, Crossover Study

“…Flavonoids are natural polyphenols that are widely found in plants [21], and NoT have many biological activities and efficacy against various diseases [10,22]. Other than LUTS, these include metabolic diseases (DM, obesity), inflammatory diseases, dermatological disorders (especially antiaging and allergies), muscle atrophy, heart failure, liver dysfunction, and dementia [12]. Because NoT have been found to increase the amplitude of oscillation in the expression of clock genes, and dysfunctions of circadian rhythm are associated with such diseases [23], NoT may confer potent protection against these diseases by modulating the circadian rhythm.…”

“…We aimed to only include nighttime as a therapeutic period and then selected 30 mg of nobiletin, which was a half-dose of 60 mg administered for healthy volunteers aged an average of 49 years in the article [13]. We adopted 30 mg of nobiletin, a higher dose than 10 mg of nobiletin, which was administered for memory impairment [12]. In another article, 2.91 mg of nobiletin (including α-linolenic acid as another ingredient) was used for participants aged 68.7 years [27].…”

“…NoT are flavonoids, a kind of polyphenol obtained from the rind of Citrus depressa, which is a type of lemon native to Okinawa in Japan, Taiwan, and China. For example, NoT has been reported to be effective for metabolic disorders [11] or memory impairment [12] as a dietary supplement, although it is not approved for medical use in clinics. From the perspective of chronobiology, a randomized clinical trial was conducted to evaluate the effectiveness and safety of NoT in patients with nocturia (NoT-nocturia study).…”