Alzheimer’s disease (AD) is a neurodegenerative disorder associated with cognitive decline. Despite worldwide efforts to find a cure, no proper treatment has been developed yet, and the only effective countermeasure is to prevent the disease progression by early diagnosis. The reason why new drug candidates fail to show therapeutic effects in clinical studies may be due to misunderstanding the cause of AD. Regarding the cause of AD, the most widely known is the amyloid cascade hypothesis, in which the deposition of amyloid beta and hyperphosphorylated tau is the cause. However, many new hypotheses were suggested. Among them, based on preclinical and clinical evidence supporting a connection between AD and diabetes, insulin resistance has been pointed out as an important factor in the development of AD. Therefore, by reviewing the pathophysiological background of brain metabolic insufficiency and insulin insufficiency leading to AD pathology, we will discuss how can insulin resistance cause AD.

Hongjam (HJ) is the steamed and freeze-dried powder of larva-stage silkworm (Bombyx mori) rich in protein, unsaturated fatty acids, and minerals. Silkworm products have traditionally been used for medical purposes, and their effectiveness in diabetic and neurodegenerative diseases has been studied. In particular, the anti-inflammatory-antioxidant, blood sugar-lowering, and neuroprotective effects are expected to be useful for the prevention and treatment of dementia, especially in a model of dementia related to insulin resistance. Most animal models of Alzheimer’s disease (AD) are based on genetic factors and research based on these models does not explain the pathophysiology of sporadic AD. Therefore, no drug can effectively delay the progression of AD. We hypothesized that HJ may improve cognitive function in an insulin resistance model which is considered one of the causes of sporadic AD. Insulin resistance was induced by a high-fat diet and streptozotocin injection. Additionally, the effect of HJ was tested in in vitro cultured hippocampal slices treated with an N-methyl-D-aspartate antagonist. At the given dose, HJ did not affect on the body weight but lowered blood glucose concentration, improved spatial memory in the Morris water maze and avoidance memory in the passive avoidance tests which was related to hippocampal brain-derived neurotrophic factor. In hippocampal slices, HJ strengthened long-term potentiation, which was suppressed by AP5. Thus, HJ improved cognitive functions in an insulin-resistance related dementia model and may be useful in treating sporadic AD.

Background/Objectives: Hytallzen™ is a natural combined extract of Artemisia princeps and Thymus vulgaris. The present study evaluated its growth-promoting effects during the rapid growth period in male Sprague–Dawley rats. Methods: Hytallzen™ (150 mg/kg/day) was orally administered for 9 weeks beginning at postnatal week 3. Growth-related parameters, including body weight, body length, food intake, serum insulin-like growth factor-1 (IGF-1), and tibia length and weight, were assessed. Results: Hytallzen™ significantly increased body weight, body length, food intake, tibia length, and tibia weight compared with controls. In addition, serum IGF-1 concentration was significantly elevated at week 6 and showed positive correlations with final body weight, body length, tibia length, and tibia weight. Conclusions: These findings suggest that Hytallzen™ is associated with favorable changes in growth-related parameters and serum IGF-1 levels in healthy growing rats, supporting its potential as a growth-supportive material under normal physiological growth conditions.