Diabetic encephalopathy (DE) is often a complication in patients with Alzheimer’s disease due to high blood sugar induced by diabetic mellitus. Ergothioneine (EGT) and hispidin (HIP) are antioxidants present in Phellinus linteus. Methylglyoxal (MGO), a toxic precursor of advanced glycated end products (AGEs), is responsible for protein glycation. We investigated whether a combination EGT and HIP (EGT + HIP) protects against MGO‐induced neuronal cell damage. Rat pheochromocytoma (PC12) cells were preincubated with EGT (2 μM), HIP (2 μM), or EGT + HIP, then challenged with MGO under high‐glucose condition (30 μM MGO + 30 mM glucose; GLU + MGO) for 24–96 h. GLU + MGO markedly increased protein carbonyls and reactive oxygen species in PC12 cells; both of these levels were strongly reduced by EGT or HIP with effects comparable to those of 100 nM aminoguanidine (an AGE inhibitor) but stronger than those of 10 μM epalrestat (an aldose reductase inhibitor). GLU + MGO significantly increased the levels of AGE and AGE receptor (RAGE) protein expression of nuclear factor kappa‐B (NF‐κB) in the cytosol, but treatment with EGT, HIP, or EGT + HIP significantly attenuated these levels. These results suggest that EGT and HIP protect against hyperglycemic damage in PC12 cells by inhibiting the NF‐κB transcription pathway through antioxidant activities.

The pigeon pea (Cajanus cajan (L.) Millsp.) is one of the major grain legume crops of the tropical world and recent evidence indicates that it possesses various health benefits. However, to the best of our knowledge, no comparison has been made on the nutritional composition and biological functions of its leaves, seeds, and roots. Therefore, the present study investigates which part of the C. cajan (L.) Millsp plant has the highest potential for development as a health food product. Results show that C. cajan (L.) Millsp roots (CCR) have a higher total polyphenol content (TPC) and total flavonoids flavonoid (TFC) contents than leaves and seeds. The antioxidant, anti-hyperglycemic, and anti-bacterial activities of CCR extracted with hot water (HWCR), 50% ethanol (EECR50), and 95% ethanol (EECR95) were determined. We found that EECR95 had the strongest antioxidant activity, as evaluated by 1,1-Diphenyl-2-picrylhydrazyl radical (DPPH) and 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS⁺) scavenging, and reducing power. EECR95 exhibited higher anti-hyperglycemic ability (inhibition of α-glucosidase and α-amylase activities) and anti-glycation effects (IC₅₀ = 39, 120 and 229 μg/mL, respectively) than HWCR and EECR50. EECR95 also exhibited potent anti-bacterial activities on E. coli, Staphylococcus aureus, Porphyromonas gingivalis, and Streptococcus mutans, with minimum inhibitory concentrations of 113, 180, 16, and 100 μg/mL, respectively. Based on above results, we conclude that CCR has considerable potential for health food development and further studies of CCR in animals to confirm these biological effects and safety issues are warranted.

Cajanus cajan (L.) Millsp., also named pigeon pea, is widely grown in the tropics and the subtropics. C. cajan roots (CR) and ribs stewed in hot water have been used as a traditional medicine in various cultures to treat diabetes. The purpose of this study was to determine the functional components of hot water (WCR) and 50%, 95% ethanol extracts (EECR50 and EECR95) from CR, then evaluating their antioxidant and anti-inflammatory effects. The results indicated that EECR95 had higher polyphenol, especially the isoflavones (e.x. daidzein, genistein, and cajanol) than those of the other extracts, and it also exhibited the most potent anti-oxidative activities by in vitro antioxidant assay. In the lipopolysaccharide-stimulated RAW 264.7 cells, we found that EECR95 significantly decreased intracellular reactive oxygen species and significantly enhanced the activities of superoxide dismutase and catalase. Mechanism studies showed that EECR95 mainly activated nuclear factor (NF) erythroid 2-related factor 2/antioxidant protein heme oxygenase-1 and inhibited nuclear factor kappa B (NF-κB) signaling pathway, and thus exhibited antioxidant and anti-inflammatory effects. Overall, this study suggests that CR may have the potential to be developed as a biomedical material and that genistein, which has relatively high uptakes (3.44% for the pure compound and 1.73% for endogenous genistein of EECR95) at 24 h of incubation with RAW 264.7 cells, could be the main active component of CR.

The pharmacological effects of the fruiting body of Ophiocordyceps sinensis (O. sinensis) such as antioxidant, anti-virus, and immunomodulatory activities have already been described, whereas the anti-inflammatory effects and active components of the submerged culture of O. sinesis (SCOS) still need to be further verified. This study aimed to investigate the active compounds in the fermented liquid (FLOS), hot water (WEOS), and 50–95% (EEOS-50, EEOS-95) ethanol extracts of SCOS and their anti-inflammatory effects and potential mechanisms in lipopolysaccharide (LPS)-stimulated microglial BV2 cells. The results demonstrated that all of the SCOS extracts could inhibit NO production in BV2 cells. EEOS-95 exhibited the strongest inhibitory effects (71% inhibitory ability at 500 µg/mL), and its ergosterol, γ-aminobutyric acid (GABA), total phenolic, and total flavonoid contents were significantly higher than those of the other extracts (18.60, 18.60, 2.28, and 2.14 mg/g, p < 0.05, respectively). EEOS-95 also has a strong inhibitory ability against IL-6, IL-1β, and TNF-α with an IC₅₀ of 617, 277, and 507 µg/mL, respectively, which is higher than that of 1 mM melatonin. The anti-inflammatory mechanism of EEOS-95 seems to be associated with the up-regulation of PPAR-γ/Nrf-2/HO-1 antioxidant-related expression and the down-regulation of NF-κB/COX-2/iNOS pro-inflammatory expression signaling. In summary, we demonstrated that EEOS-95 exhibits neuroinflammation-mediated neurodegenerative disorder activities in LPS-induced inflammation in brain microglial cells.

Cajanus cajan (L.) Millsp., also known as pigeon pea, has roots that have exhibited much pharmacological potential. The present study was conducted to assess the safe dose of the ethanolic extract of C. cajan roots (EECR95) and to analyze the main soy isoflavones contents. In vitro, we investigated the mutagenicity and cytotoxic effect of EECR95 on Salmonella typhimurium-TA98 and TA100 (by Ames tests) and RAW 264.7, L-929, and HGF-1 cell lines (by MTT tests) for 24 h of incubation. We found no mutagenic or cytotoxic effects of EECR95. After administration of 0.2 or 1.0 g/kg bw of EECR95 to both male and female Wistar rats for 90 days, there were no significant adverse effects on the behaviors (body weight, water intake, and food intake), organ/tissue weights, or immunohistochemical staining, and the urine and hematological examinations of the rats were within normal ranges. EECR95 potentially decreases renal function markers in serum (serum uric acid, BUN, CRE, and GLU) or liver function markers (cholesterol, triglyceride, and glutamic-pyruvate-transaminase (GPT)). We also found that EECR95 contained five soy isoflavones (genistein, biochanin A, daidzein, genistin, and cajanol), which may be related to its hepatorenal protection. Based on the high dose (1.0 g/kg bw) of EECR95, a safe daily intake of EECR95 for human adults is estimated to be 972 mg/60 kg person/day.

Cajanus cajan (L.) Millsp., known as pigeon pea, C. cajan (L.) Millsp. roots (CR) contain daidzein, genistein, and cajanol which have numerous health benefits. The aim of this study was to investigate the anti-proliferative and anti-metastatic effects of sub-fractions (EECRpw, EECRp25, EECRp50, EECRp70, and EECRp95) containing 95% ethanol extract from CR (EECR95) in oral squamous cell carcinoma cells (SCC25). We found that the sub-fraction (EECRp70) significantly inhibited cell proliferation, and down-regulated secretion of matrix metalloproteinase-2 and vascular endothelial growth factor-2 in a dose-dependent manner, and the mechanisms were related to down-regulated iNOS/COX-2/NF-ĸB signaling pathways. Moreover, EECRp70 in combination with a cancer chemotherapeutic agent (cisplatin or taxol) also blocked cell proliferation, arrested cell cycle in subG1 phase, inhibited intracellular production of reactive oxygen species, and reduced migration and invasion of SCC25 cells. Furthermore, our results demonstrate that EECRp70 inhibits proliferation and metastatic, which is related to the relatively high uptake of genistein of EECRp70 (2.71%) in SCC25 cells for 12 h. In addition, EECRp70 contains abundant flavonoids such as genistein and cajanol. Thus, we suggest that the study supports the anecdotal use of CR in herbal medicine and functional food.