Ophiocordyceps formosana improves hyperglycemia and depression-like behavior in an STZ-induced diabetic mouse model

Abstract

BackgroundA newly defined Cordyceps species, Ophiocordyceps formosana (O. formosana) has been implicated in multitudinous bioactivities, including lowering glucose and cholesterol levels and modulating the immune system. However, few literatures demonstrate sufficient evidence to support these proposed functions. Although the use of Cordyceps spp. has been previously addressed to improve insulin insensitivity and improve the detrimental symptoms of depression; its mechanistic nature remains unsettled. Herein, we reveal the effects of O. formosana in ameliorating hyperglycemia accompanied with depression.MethodsDiabetes was induced in mice by employing streptozotocin(STZ), a chemical that is toxic to insulin-producing β cells of the pancreas. These streptozotocin (STZ)-induced diabetic mice showed combined symptoms of hyperglycemia and depressive behaviors. Twenty-four STZ-induced mice were randomly divided into 3 groups subjected to oral gavage with 100 μL solution of either PBS or 25 mg/mL Ophiocordyceps formosana extract (OFE) or 2 mg/mL rosiglitazone (Rosi, positive control group). Treatments were administered once per day for 28 days. An additional 6 mice without STZ induction were treated with PBS to serve as the control group. Insulin sensitivity was measured by a glucose tolerance test and levels of adiponectin in plasma and adipose tissue were also quantified. Behavioral tests were conducted and levels of monoamines in various brain regions relating to depression were evaluated.ResultsHPLC analysis uncovered three major constituents, adenosine, D-mannitol and cordycepin, within O. formosana similar to other prestigious medicinal Cordyceps spp.. STZ-induced diabetic mice demonstrated decreased body weight and subcutaneous adipose tissue, while these symptoms were recovered in mice receiving OFE treatment. Moreover, the OFE group displayed improved insulin sensitivity and elevated adiponectin within the plasma and adipose tissue. The anti-depressive effect of OFE was observed in various depression-related behavior tests. Concurrently, neurotransmitters, like 5-HT and dopamine in the frontal cortex, striatum and hippocampus were found to be up-regulated in OFE-treated mice.ConclusionsOur findings illustrated, for the first time, the medicinal merits of O. formosana on Type I diabetes and hyperglycemia-induced depression. OFE were found to promote the expression of adiponectin, which is an adipokine involved in insulin sensitivity and hold anti-depressive effects. In addition, OFE administration also displayed altered levels of neurotransmitters in certain brain regions that may have contributed to its anti-depressive effect. Collectively, this current study provided insights to the potential therapeutic effects of O. formosana extracts in regards to hyperglycemia and its depressive complications.

Pathophysiology linking depression and type 2 diabetes: Psychotherapy, physical exercise, and fecal microbiome transplantation as damage control

“…cortex, and striatum, and also diminished depressive behavior (Huang et al, 2016). The amygdala is associated with emotion, fear, motivation, and reward (Janak & Tye, 2015) and is implicated in diabetes-associated cognitive and mood disturbances (McNay, 2015).…”

“…Targeting inflammation by using traditional herbs, such as the Cordyceps species, is found to be beneficial. Its administration in hyperglycemic mice reversed the depletion of dopamine and 5‐HT levels in the hippocampus, frontal cortex, and striatum, and also diminished depressive behavior (Huang et al., 2016). The amygdala is associated with emotion, fear, motivation, and reward (Janak & Tye, 2015) and is implicated in diabetes‐associated cognitive and mood disturbances (McNay, 2015).…”

LC/ESI/TOF-MS Characterization, Anxiolytic and Antidepressant-like Effects of Mitragyna speciosa Korth Extract in Diabetic Rats

“…The results from this study revealed that DM led to characteristic anxiety and depressive-like behaviors, as indicated by the increase in immobility duration (FST), decrease in entries and time spent in the open arms (EPMT) as well as reduction in the number of crossing and rearing (OFT), which were in corroboration with previous studies on DM-induced anxiety and depression [ 8 , 26 , 31 , 32 ]. Metabolic disorders, including diabetes and obesity, have been prominently associated a number of psychological problems particularly major depressive disorders and anxiety, and hyperglycemia is a prevalent factor that can modulate the onset, progression and deterioration of depression and anxiety [ 33 ]. MSE treatment notably decreased the duration of immobility in the FST.…”

The impact of insulin on the serotonergic system and consequences on diabetes‐associated mood disorders

“…36,37 These behavioural anomalies are not restricted to T2D because STZ injection-induced T1D in mice also promotes anxiety and depressive-like symptoms. [38][39][40] Conversely, animal studies have shown that chronic mild stress-, social defeat-or dexamethasone-induced depressive-like symptoms are correlated with peripheral insulin resistance. [40][41][42] Nevertheless, in these models, it has not been shown whether metabolic impairments precede or cause mood abnormalities.…”