Effects of Dendrobium officinale on chronic fatigue in rats: Modulation of tryptophan metabolism 2026 Yan et al

[Andy]

Ethnopharmacological relevance​

Chronic fatigue is a prolonged and persistent state of mental and physical exhaustion that is not readily relieved by rest. Dendrobium officinale Kimura & Migo (D. officinale), a traditional tonic medicinal and edible herb, which have been reported to possess diverse pharmacological activities, including anti-fatigue, immunomodulatory, and gut microbiota-modulating effects. Nevertheless, the effects and underlying mechanisms on chronic fatigue remain largely unexplored.

Aim of the study​

This study aimed to evaluate the effects of D. officinale in a rat model of chronic fatigue induced by complex poor lifestyles, and to elucidate the underlying mechanisms via tryptophan (TRP) metabolic modulation.

Materials and methods​

A rat model of chronic fatigue was established through complex poor lifestyles, including over stress, inadequate sleep, irregular diet, and over work. The animals were then randomly allocated into five groups: a normal control group (NC), a model control group (MC), and three groups treated with D. officinale water extract (DOW) at doses of 0.1, 0.2, and 0.4 g/kg via oral gavage. After a 4-week intervention, the effects of DOW were subjected by general sign observation, swimming test, elevated plus maze (EPM) and open field tests (OFT). Furthermore, 16S rRNA gene sequencing, LC–MS analysis, Western blotting (WB), and quantitative real-time PCR (qRT-PCR) were performed to assess gut microbiota composition, TRP metabolites, and key metabolic enzymes, thereby elucidating the potential mechanisms by which DOW ameliorates chronic fatigue.

Results​

DOW markedly improved exercise endurance, alleviated depression-like behaviour as well as attenuated dysregulation of the neuroendocrine–immune (NEI) system. In addition, DOW modulated gut microbiota disturbances and substantially increased the levels of TRP-derived indole metabolites, including indole (IDN), indole-3-acetic acid (IAA), indole-3-propionic acid (IPA), and indole-3-aldehyde (IAld). Meanwhile, it restored the inhibited kynurenine (KYN) metabolic pathway and promoted hepatic expression of key KYN-pathway enzymes, including tryptophan 2,3-dioxygenase 2 (TDO2), kynurenine 3-monooxygenase (KMO), and kynurenine aminotransferase 1 (KAT1), thereby enhancing the production of downstream KYN metabolite, including 3-Hydroxyanthranilic acid (3-HAA), Quinolinic acid (QA), Picolinic acid (PA), and Xanthurenic acid (XA). Correlation analysis further demonstrated that the alleviation of chronic-fatigue–related symptoms and behavioral abnormalities by DOW was strongly associated with its regulation of TRP metabolism.

Conclusion​

DOW effectively alleviated chronic fatigue induced by complex poor lifestyles in rats, and its underlying mechanism may involve modulating the gut microbiota to enhance the synthesis of indole-derived metabolites, and upregulating the expression of key enzymes in the KYN pathway to promote the generation of KYN-derived metabolites, thereby restoring TRP metabolic homeostasis.

Paywall

 

[rvallee]

A rat model of chronic fatigue was established through complex poor lifestyles, including over stress, inadequate sleep, irregular diet, and over work

But that's a model of stress, not fatigue. Chronic fatigue is not the result of lifestyle behavior, otherwise it wouldn't be chronic.

 

[Peter T]

But that's a model of stress, not fatigue. Chronic fatigue is not the result of lifestyle behavior, otherwise it wouldn't be chronic.

Unless I am misremembering a relatively recent couple of studies also in China looking at chronic fatigue syndrome (CFS) in students often report unexpectedly high incidence rates suggest they are also confounding lifestyle issues with chronic fatigue which they also confuse with CFS.

 

[rvallee]

Unless I am misremembering a relatively recent couple of studies also in China looking at chronic fatigue syndrome (CFS) in students often report unexpectedly high incidence rates suggest they are also confounding lifestyle issues with chronic fatigue which they also confuse with CFS.

I'm not really thinking about differentiating from ME/CFS. Even as a model of generic chronic fatigue this is wrong, because it would be alleviated with rest, with reducing the problem, which is stress. This is more like someone who is very tired after a long day of physical labor, except happening every day, or something like it. It's a model of acute fatigue that is renewed, perpetuated. It would be like a model of chronic pain where people put a Lego brick in their shoes, have to walk on it every day, makes no sense.

It's so damn annoying how the fact that medicine is all over the place with even basic definitions is used against us as if we're responsible for the toxic environment they create for us.