Pilot Study: Nutritional and Preclinical Safety Investigation of Fermented Hispidin-Enriched Sanghuangporus sanghuang Mycelia: A Promising Functional Food Material to Improve Sleep

Abstract

Sleep disturbances have been the hallmark of the recent coronavirus disease 2019 pandemic. Studies have shown that once sleep is disrupted, it can lead to psychological and physical health issues which can, in turn, disrupt circadian rhythm and induce further sleep disruption. As consumers are trying to establish healthy routines, nutritional and preclinical safety investigation of fermented hispidin-enriched Sanghuangporus sanghuang mycelia (GKSS) as a novel food material for spontaneous sleep in Sprague-Dawley rats is conducted for the first time. Results showed that the nutritional analysis of GKSS including moisture, ash, crude lipid, crude protein, carbohydrate, and energy were found to be 2.4 ± 0.3%, 8.0 ± 2.5%, 1.7 ± 0.3%, 22.9 ± 1.2%, 65.1 ± 3.1%, and 367.1 ± 10.2 kcal/100 g respectively. In the 28-day repeated-dose oral toxicity study, only Sprague-Dawley male rats receiving 5 g/kg showed a slight decrease in feed consumption at week 3, but no associated clinical signs of toxicity or significant weight loss were observed. Although a significant reduction of the platelet count was found in mid- and high-dose GKSS treated male groups, such changes were noted to be within the normal range and were not correlated with relative spleen weight changes. Hence, the no observed adverse effect level (NOAEL) of GKSS was identified to be higher than 5 g/kg in rats. After the safety of GKSS is confirmed, the sleep-promoting effect of GKSS ethanolic extract enriched with hispidin was further assessed. Despite 75 mg/kg of GKSS ethanolic extract does not affect wakefulness, rapid eye movement (REM) sleep and non-REM (NREM) sleep, GKSS ethanolic extract at 150 mg/kg significantly decreased wakefulness and enhanced NREM and REM sleep. Interestingly, such effects seem to be mediated through anti-inflammatory activities via NF-E2-related factor-2 (Nrf2) signaling pathway. Taken together, these findings provide the preliminary evidence to studies support the claims suggesting that GKSS contained useful phytochemical hispidin could be considered as and is safe to use as a functional food agent or nutraceutical for relieving sleep problems mediated by Nrf2 pathway, which the results are useful for future clinical pilot study.

Research Progress of Bioactive Components in Sanghuangporus spp.

“…Sanghuangporus spp., also known as Phellinus or Inonotus in some of the literature and some areas worldwide, is a perennial genus of edible mushrooms widely distributed in boreal forests in East Asia, especially in subtropical and tropical areas, holding profound pharmaceutical potential [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 ]. These medicinal mushrooms, as illustrated in Figure 1 , have been popular in oral use since ancient times in countries such as China, Korea, and Japan [ 4 , 5 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 ].…”

“…Entering modern times, pharmaceutical research has demonstrated multiple functions of Sanghuangporus spp., including the ability to improve blood circulation, scavenge free radicals, demonstrate anti-inflammatory effects, anti-carcinogenesis, antioxidative abilities, immunomodulatory effects, antidiabetic activities, antimicrobial abilities, and antiaging effects [ 2 , 4 , 9 , 14 , 20 , 21 , 22 , 24 , 25 , 26 , 27 , 28 , 29 ]. Some research has also provided evidence of antigout, sleep-improving, neuroprotective, and hepatoprotective activities [ 3 , 30 , 31 , 32 ]. Despite their prolonged use in history, research progress on the application of these mushrooms has been slow, mainly due to the following factors.…”

“…But they are also marked by disadvantages, such as long extraction times, low purity or yield, and possible contamination of the environment, which have given rise to some new yet more expensive methods, such as the deep eutectic solvent (DES) method [ 43 ]. The mycelia are often acquired through liquid fermentation [ 15 ], after which they are used to extract single components, total components, or used as mycelia extracts using the methods mentioned above [ 3 , 32 , 37 , 44 , 45 , 46 ]. These extracts can be used to study their effects as a whole or further purified using traditional columns, synthetic polymers, or microporous resin, which are discussed in detail in the purification section.…”

Hispidin‐enriched Sanghuangporus sanghuang mycelia SS‐MN4 ameliorate disuse atrophy while improving muscle endurance

“…Among the phytochemical constituents of S. sanghuang —hispidin, the yellow polyphenol pigment, displayed excellent antioxidant and anti‐obesity properties 15 . In our previous study, we observed that hispidin‐enriched S. sanghuang can upregulate nuclear factor erythroid 2‐related factor 2 (Nrf2) in a dosage‐dependent manner 16 . Deficiency of Nrf2 expression has been reported as a vital marker associated with sarcopenia development in vivo 17 .…”

“…15 In our previous study, we observed that hispidin-enriched S. sanghuang can upregulate nuclear factor erythroid 2-related factor 2 (Nrf2) in a dosage-dependent manner. 16 Deficiency of Nrf2 expression has been reported as a vital marker associated with sarcopenia development in vivo. 17 Clinical study also showed that the Nrf2-antioxidant response element (ARE) pathway is impaired in older adults (63 ± 1 years) and the benefit of exercising is less effective when compared with the young adult (23 ± 1 years).…”