Tag: herbal medicine

Potential application of brain-gut axis-based treatments in Long COVID and ME/CFS: a case-based systematic review

Abstract:

Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and Long COVID share clinical features including persistent fatigue, post-exertional malaise (PEM), and gastrointestinal (GI) dysfunction. Growing evidence implicates brain-gut axis dysregulation, characterized by dysbiosis, neuroinflammation within the central nervous system (CNS), increased intestinal permeability, and microbial translocation in their pathophysiology. However, therapeutic strategies targeting these pathways remain poorly defined.

Methods: We report a case of post-COVID ME/CFS successfully treated with electroacupuncture (EA)-based deep peroneal nerve stimulation which was employed to potentiate the vagal reflex. Fatigue trajectories were assessed using the Multidimensional Fatigue Inventory over 12 weeks. Based on the case, a systematic review of randomized controlled trials (RCTs) evaluating brain-gut axis-modulating interventions in ME/CFS or Long COVID was conducted.

Results: The patient exhibited a significant reduction in total fatigue, with early improvements in motivation and mental fatigue, and delayed improvement in physical fatigue following transient systemic symptom flares. Across included RCTs (n = 8, 790 participants), four investigated gut microbiome-modulating therapies and four employed nerve stimulation. Synbiotic and herbal interventions demonstrated benefits for fatigue or PEM, accompanied by alterations in specific bacterial populations or CNS metabolisms. Regarding nerve stimulation, transcranial direct current stimulation (tDCS) combined with exercise program improved fatigue, whereas standalone tDCS, auricular or peripheral TENS showed limited efficacy.

Conclusion: Brain-gut axis-based interventions may alleviate fatigue in ME/CFS and Long COVID by potentially modulating neuroinflammation, restoring microbiome balance, and improving epithelial barrier function. EA-based vagal stimulation represents a feasible option for patients with severe or treatment-resistant symptoms. Larger mechanistic studies and rigorously designed RCTs are needed to establish therapeutic targets and optimize intervention strategies.

Source: Kim DY, Youn J, Kang N, Cho SI, Ha IH. Potential application of brain-gut axis-based treatments in Long COVID and ME/CFS: a case-based systematic review. J Transl Med. 2026 Feb 10. doi: 10.1186/s12967-026-07807-w. Epub ahead of print. PMID: 41668172. https://link.springer.com/article/10.1186/s12967-026-07807-w (Full text available as PDF file)

Recovery from Myalgic Encephalomyelitis/Chronic Fatigue syndrome developed after severe acute respiratory syndrome coronavirus 2 vaccination: A case report

Abstract:

Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a neurological adverse effect after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccinations. However, clinicians do not recognize the condition well, and no case report has shown a full recovery.

Case presentation: We present a 65-year-old Japanese female who experienced severe fatigue, postexertional malaise, orthostatic intolerance, and various symptoms after her third SARS-CoV-2 vaccination. Following thorough examinations and excluding other potential diagnoses, she met the diagnostic criteria for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). The symptoms persisted for 30 months and improved ultimately with comprehensive treatment and a self-management strategy, including pacing management, pharmacological treatments, and psychiatric interventions to support those struggling with the despair over the devastating symptoms.

Conclusion: This case report describes ME/CFS following the SARS-CoV-2 vaccination and its full recovery. It illustrates the importance of considering the differential diagnosis of psychiatric disorders and addressing the condition through psychiatric interventions. Our findings provide new insights into treating ME/CFS and the vaccination-related adverse effects.

Source: Kurotori I, Sasao W, Abe M. Recovery from Myalgic Encephalomyelitis/Chronic Fatigue syndrome developed after severe acute respiratory syndrome coronavirus 2 vaccination: A case report. PCN Rep. 2025 Apr 27;4(2):e70111. doi: 10.1002/pcn5.70111. PMID: 40291166; PMCID: PMC12034265. https://pmc.ncbi.nlm.nih.gov/articles/PMC12034265/ (Full text)

Herbal Medicines for Long COVID: A Phase 2 Pilot Clinical Study

Abstract:

Background: Infections of Coronavirus Disease-2019 (COVID-19) can cause long-term effects known as long COVID. This pilot study aimed to evaluate the feasibility of a clinical study as well as the efficacy and safety of traditional East Asian herbal medicines in alleviating fatigue and cognitive dysfunction “brain fog” in patients with long COVID.

Methods: This prospective pilot study investigated the use of three types of herbal medicines, Bojungikki-tang (BIT), Kyungok-go (KOG), and Cheonwangbosim-dan (CBD), for a 12-week period as potential treatments for fatigue and cognitive dysfunction in patients with long COVID. Forty-five patients with long COVID were recruited, and one of three drugs was given based on the patient’s symptoms and pattern identification. The effect of herbal medications on fatigue and cognitive function outcomes was assessed over a 36-week period, with patient adherence closely monitored.

Results: After 12 weeks of herbal drug administration, fatigue symptoms improved significantly across all groups, with treatment success rates of 80%, 53.33%, and 46.67% in the BIT, KOG, and CBD groups, respectively. However, “brain fog” symptoms showed less improvement, with treatment success rates of 40%, 46.67%, and 13.33% in the BIT, KOG, and CBD groups, respectively. All adverse events reported were mild and unrelated to the medication. The study design was found to be feasible with high medication adherence.

Conclusions: This study demonstrated the feasibility of conducting a clinical trial with three herbal medicines to treat long COVID symptoms like fatigue and “brain fog.”

Source:Kim, T.; Yoon, J.; Kim, S.; Kang, B.; Kang, J.W.; Kwon, S. Herbal Medicines for Long COVID: A Phase 2 Pilot Clinical Study. Preprints 2024, 2024011605. https://doi.org/10.20944/preprints202401.1605.v1 https://www.preprints.org/manuscript/202401.1605/v1 (Full text available as PDF file)

The potential role of Rhodiola rosea L. extract WS® 1375 for patients with post-COVID-19 fatigue

Abstract:

Fatigue and physical exhaustion are the dominant symptoms of post-coronavirus (COVID-19) conditions that might even develop after only mild acute disease. Post-acute infection syndromes have been observed after various infections, e.g., Coxiella burnetii, Ebola, Dengue, Polio, severe acute respiratory syndrome (SARS), Chikungunya, West Nile Virus, Borrelia, or Giardina lamblia. The similarities in symptoms and courses suggest a high likelihood of common pathogenetic pathways, including persistent infection, autoimmune reactions, dysregulation of the microbiome, inability to repair tissue damage, or endothelial dysfunction.

Some herbal drugs, so-called adaptogens, exert effects resulting in an increase in the resistance or regulatory potential of organisms against biological, chemical and physical burden or stress. Therefore, it seems possible that adaptogens can be helpful in cases of post-COVID-19 symptoms. One of these adaptogens is Rhodiola rosea L. The proprietary ethanolic extract made from roots and rhizomes of Rhodiola rosea WS® 1375 has been reported to modulate neuroinflammation in response to stress stimuli in preclinical models. Moreover, it activated the synthesis or resynthesis of adenosine triphosphate (ATP) in skeletal muscle mitochondria and counteracted muscle fatigue.

In three clinical trials with subjects suffering from burnout symptoms, prolonged or chronic fatigue symptoms or life-stress symptoms, clinically relevant improvements of fatigue and exhaustion were reported over 4 to 12 weeks of treatment at a very favorable tolerability and safety profile in heterogeneous patient populations. In conclusion, Rhodiola rosea extract WS® 1375 has a promising pharmacological and therapeutic profile for the treatment of fatigue and physical exhaustion associated with post-COVID-19 conditions.

Source: Wegener T, Edwards D, Kasper S. The potential role of Rhodiola rosea L. extract WS® 1375 for patients with post-COVID-19 fatigue. hb TIMES Schw Aerztej. 2023;8(1):56-61. doi:10.36000/hbT.2023.09.001 https://schw-aerztej.healthbooktimes.org/article/74319-the-potential-role-of-rhodiola-rosea-l-extract-ws-1375-for-patients-with-post-covid-19-fatigue (Full text)

Ginkgo Biloba and Long COVID: In Vivo and In Vitro Models for the Evaluation of Nanotherapeutic Efficacy

Abstract:

Coronavirus infections are neuroinvasive and can provoke injury to the central nervous system (CNS) and long-term illness consequences. They may be associated with inflammatory processes due to cellular oxidative stress and an imbalanced antioxidant system. The ability of phytochemicals with antioxidant and anti-inflammatory activities, such as Ginkgo biloba, to alleviate neurological complications and brain tissue damage has attracted strong ongoing interest in the neurotherapeutic management of long COVID.
Ginkgo biloba leaf extract (EGb) contains several bioactive ingredients, e.g., bilobalide, quercetin, ginkgolides A–C, kaempferol, isorhamnetin, and luteolin. They have various pharmacological and medicinal effects, including memory and cognitive improvement. Ginkgo biloba, through its anti-apoptotic, antioxidant, and anti-inflammatory activities, impacts cognitive function and other illness conditions like those in long COVID. While preclinical research on the antioxidant therapies for neuroprotection has shown promising results, clinical translation remains slow due to several challenges (e.g., low drug bioavailability, limited half-life, instability, restricted delivery to target tissues, and poor antioxidant capacity).
This review emphasizes the advantages of nanotherapies using nanoparticle drug delivery approaches to overcome these challenges. Various experimental techniques shed light on the molecular mechanisms underlying the oxidative stress response in the nervous system and help comprehend the pathophysiology of the neurological sequelae of SARS-CoV-2 infection.
To develop novel therapeutic agents and drug delivery systems, several methods for mimicking oxidative stress conditions have been used (e.g., lipid peroxidation products, mitochondrial respiratory chain inhibitors, and models of ischemic brain damage). We hypothesize the beneficial effects of EGb in the neurotherapeutic management of long-term COVID-19 symptoms, evaluated using either in vitro cellular or in vivo animal models of oxidative stress.
Source: Akanchise T, Angelova A. Ginkgo Biloba and Long COVID: In Vivo and In Vitro Models for the Evaluation of Nanotherapeutic Efficacy. Pharmaceutics. 2023; 15(5):1562. https://doi.org/10.3390/pharmaceutics15051562 https://www.mdpi.com/1999-4923/15/5/1562 (Full text)

Panax ginseng improves physical recovery and energy utilization on chronic fatigue in rats through the PI3K/AKT/mTOR signalling pathway

Abstract:

Context: Panax ginseng C. A. Meyer (Araliaceae) is a tonic herb used in ancient Asia.

Objective: This study investigated the antifatigue effect of P. ginseng on chronic fatigue rats.

Materials and methods: Sprague-Dawley rats were divided into control, model and EEP (ethanol extraction of P. ginseng roots) (50, 100 and 200 mg/kg) groups (n = 8). The rats were subcutaneously handled with loaded swimming once daily for 26 days, except for the control group. The animals were intragastrically treated with EEP from the 15th day. On day 30, serum, liver and muscles were collected, and the PI3K/Akt/mTOR signalling pathway was evaluated.

Results: The swimming times to exhaust of the rats with EEP were significantly longer than that without it. EEP spared the amount of muscle glycogen, hepatic glycogen and blood sugar under the chronic state. In addition, EEP significantly (p < 0.05) decreased serum triglycerides (1.24 ± 0.17, 1.29 ± 0.04 and 1.20 ± 0.21 vs. 1.58 ± 0.13 mmol/L) and total cholesterol (1.64 ± 0.36, 1.70 ± 0.15 and 1.41 ± 0.19 vs. 2.22 ± 0.19 mmol/L) compared to the model group. Regarding the regulation of energy, EEP had a positive impact on promoting ATPase activities and relative protein expression of the PI3K/Akt/mTOR pathway.

Conclusions: Our results suggested that EEP effectively relieved chronic fatigue, providing evidence that P. ginseng could be a potential dietary supplement to accelerate recovery from fatigue.

Source: Zhang G, Lu B, Wang E, Wang W, Li Z, Jiao L, Li H, Wu W. Panax ginseng improves physical recovery and energy utilization on chronic fatigue in rats through the PI3K/AKT/mTOR signalling pathway. Pharm Biol. 2023 Dec;61(1):316-323. doi: 10.1080/13880209.2023.2169719. PMID: 36695132; PMCID: PMC9879180. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9879180/ (Full text)

Chinese herbal medicine for the treatment of chronic fatigue syndrome: A systematic review and meta-analysis

Abstract:

Objectives: This meta-analysis aimed to assess the effectiveness and safety of Chinese herbal medicine (CHM) in treating chronic fatigue syndrome (CFS).

Methods: Nine electronic databases were searched from inception to May 2022. Two reviewers screened studies, extracted the data, and assessed the risk of bias independently. The meta-analysis was performed using the Stata 12.0 software.

Results: Eighty-four RCTs that explored the efficacy of 69 kinds of Chinese herbal formulas with various dosage forms (decoction, granule, oral liquid, pill, ointment, capsule, and herbal porridge), involving 6,944 participants were identified. This meta-analysis showed that the application of CHM for CFS can decrease Fatigue Scale scores (WMD: –1.77; 95%CI: –1.96 to –1.57; p < 0.001), Fatigue Assessment Instrument scores (WMD: –15.75; 95%CI: –26.89 to –4.61; p < 0.01), Self-Rating Scale of mental state scores (WMD: –9.72; 95%CI:–12.26 to –7.18; p < 0.001), Self-Rating Anxiety Scale scores (WMD: –7.07; 95%CI: –9.96 to –4.19; p < 0.001), Self-Rating Depression Scale scores (WMD: –5.45; 95%CI: –6.82 to –4.08; p < 0.001), and clinical symptom scores (WMD: –5.37; 95%CI: –6.13 to –4.60; p < 0.001) and improve IGA (WMD: 0.30; 95%CI: 0.20–0.41; p < 0.001), IGG (WMD: 1.74; 95%CI: 0.87–2.62; p < 0.001), IGM (WMD: 0.21; 95%CI: 0.14–0.29; p < 0.001), and the effective rate (RR = 1.41; 95%CI: 1.33–1.49; p < 0.001). However, natural killer cell levels did not change significantly. The included studies did not report any serious adverse events. In addition, the methodology quality of the included RCTs was generally not high.

Conclusion: Our study showed that CHM seems to be effective and safe in the treatment of CFS. However, given the poor quality of reports from these studies, the results should be interpreted cautiously. More international multi-centered, double-blinded, well-designed, randomized controlled trials are needed in future research.

Source: Zhang, Jin, Wei, Jin, Xie, Pan and Shen. Chinese herbal medicine for the treatment of chronic fatigue syndrome: A systematic review and meta-analysis. Front. Pharmacol., 29 September 2022. Sec. Ethnopharmacology https://doi.org/10.3389/fphar.2022.958005 https://www.frontiersin.org/articles/10.3389/fphar.2022.958005/full (Full text)

Complementary and Alternative Medicine for Long COVID: Scoping Review and Bibliometric Analysis

Abstract:

Prolonged symptoms after the clearance of acute coronavirus disease 2019 (COVID-19) infection, termed long COVID, are an emerging threat to the post-COVID-19 era. Complementary and alternative medicine (CAM) interventions may play a significant role in the management of long COVID. The present study aimed to identify published studies on the use of CAM interventions for long COVID and provide an overview of the research status using bibliometric analysis.

The present scoping review searched MEDLINE, Embase, and Cochrane Library from inception until November 2021 and identified published studies on CAM interventions for long COVID. A narrative analysis of the study types and effectiveness and safety of the CAM interventions are presented and a bibliometric analysis of citation information and references of the included publications were analyzed using the Bibliometrix package for R. An electronic database search identified 16 publications (2 clinical studies and 14 study protocols of systematic reviews or clinical studies) that were included in the present study. Dyspnea or pulmonary dysfunction, quality of life, olfactory dysfunction, and psychological symptoms after COVID-19 infection were assessed in the included publications.

The two clinical studies suggested that Chinese herbal medications were effective in relieving symptoms of pulmonary dysfunction. Bibliometric analysis revealed the current trend of research publication in this area was driven by study protocols written by Chinese, Korean, and Indian authors. Thus, the present scoping review and bibliometric analysis revealed that there are few studies published about the use of CAM for long COVID and long-term management for COVID-19 survivors. Original studies on CAM interventions, including randomized controlled trials and systematic reviews, are required to actively support evidence for their use in the management of long COVID. PROSPERO registration: this trial is registered with CRD42021281526.

Source: Tae-Hun Kim, Sae-Rom Jeon, Jung Won Kang, Sunoh Kwon, “Complementary and Alternative Medicine for Long COVID: Scoping Review and Bibliometric Analysis“, Evidence-Based Complementary and Alternative Medicine, vol. 2022, Article ID 7303393, 7 pages, 2022. https://doi.org/10.1155/2022/7303393 https://www.hindawi.com/journals/ecam/2022/7303393/ (Full text)

Study on the active components and mechanism of Suanzaoren decoction in improving cognitive impairment caused by sleep deprivation

Abstract:

Ethnopharmacological relevance: Suanzaoren Decoction (SZRD) is a traditional and classic prescription for the treatment of insomnia, with a history of more than 1,000 years. It replenishes blood components, calms the nerves, reduces fever and irritability. It is commonly used in the clinical treatment of chronic fatigue syndrome, cardiac neurosis, and menopausal syndromes. Modern pharmacological studies have shown that it improves cognitive impairment; however, its mechanism of action remains unclear.

Aim of the study: This study preliminarily investigated the potential bioactive components and mechanism of SZRD in improving cognitive impairment by exploring network pharmacology, molecular docking, and conducting in vivo experiments.

Materials and methods: The components of various Chinese herbs in SZRD and their disease-related targets were identified through network pharmacology and literature. Gene ontology (GO) function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses of intersection targets were performed using the relevant database. Next, the “Components-Targets-Pathways” (C-T-P) and “Protein-Protein interaction” networks were constructed using the enrichment analysis results to further identify potential pathways, bioactive components, and hub genes. At the same time, molecular docking was used to further distinguish the key bioactive components and genes of SZRD responsible for improving cognitive impairment. Finally, the potential mechanism of action was further analysed and verified using in vivo experiments.

Results: A total of 117 potential active components and 138 intersection targets were identified by network pharmacology screening. The key bioactive components, including calycosin, 5-Prenylbutein, licochalcone G, glypallichalcone, and ZINC189892, were identified by analysing the networks and molecular docking results. Hub genes included ACHE, CYP19A1, EGFR, ESR1, and ESR2. The oestrogen signalling pathway was the most important in the enrichment analysis. In vivo experiments further proved that SZRD could improve cognitive impairment by affecting the oestrogen signalling pathway and the expression of ACHE and CYP19A1.

Conclusions: Network pharmacology and in vivo experiments demonstrate that SZRD improves cognitive impairment caused by sleep disturbance through estrogen receptor pathway, which provides a basis for its clinical application.

Source: Cheng L, Wang F, Li ZH, Wen C, Ding L, Zhang SB, You QY. Study on the active components and mechanism of Suanzaoren decoction in improving cognitive impairment caused by sleep deprivation. J Ethnopharmacol. 2022 Jun 28:115502. doi: 10.1016/j.jep.2022.115502. Epub ahead of print. PMID: 35777606. https://www.sciencedirect.com/science/article/abs/pii/S0378874122005414 (Full text)

Efficacy of Adaptogens in Patients with Long COVID-19: A Randomized, Quadruple-Blind, Placebo-Controlled Trial

Abstract:

Currently, no effective treatment of comorbid complications or COVID-19 long-haulers during convalescence is known. This randomized, quadruple-blind, placebo-controlled trial aimed to assess the efficacy of adaptogens on the recovery of patients with Long COVID symptoms. One hundred patients with confirmed positive SARS-CoV-2 test, discharged from COVID Hotel isolation, Intensive Care Unit (ICU), or Online Clinics, and who experienced at least three of nine Long COVID symptoms (fatigue, headache, respiratory insufficiency, cognitive performance, mood disorders, loss of smell, taste, and hair, sweatiness, cough, pain in joints, muscles, and chest) in the 30 days before randomization were included in the study of the efficacy of Chisan®/ADAPT-232 (a fixed combination of adaptogens Rhodiola, Eleutherococcus, and Schisandra) supplementation for two weeks.

Chisan® decreased the duration of fatigue and pain for one and two days, respectively, in 50% of patients. The number of patients with lack of fatigue and pain symptoms was significantly less in the Chisan® treatment group than in the placebo group on Days 9 (39% vs. 57%, pain relief, p = 0.0019) and 11 (28% vs. 43%, relief of fatigue, * p = 0.0157). Significant relief of severity of all Long COVID symptoms over the time of treatment and the follow-up period was observed in both groups of patients, notably decreasing the level of anxiety and depression from mild and moderate to normal, as well as increasing cognitive performance in patients in the d2 test for attention and increasing their physical activity and workout (daily walk time).

However, the significant difference between placebo and Chisan® treatment was observed only with a workout (daily walk time) and relieving respiratory insufficiency (cough). A clinical assessment of blood markers of the inflammatory response (C-reactive protein) and blood coagulation (D-dimer) did not reveal any significant difference over time between treatment groups except significantly lower IL-6 in the Chisan® treatment group. Furthermore, a significant difference between the placebo and Chisan® treatment was observed for creatinine: Chisan® significantly decreased blood creatinine compared to the placebo, suggesting prevention of renal failure progression in Long COVID. In this study, we, for the first time, demonstrate that adaptogens can increase physical performance in Long COVID and reduce the duration of fatigue and chronic pain. It also suggests that Chisan®/ADAPT-232 might be useful for preventing the progression of renal failure associated with increasing creatinine.

Source: Karosanidze I, Kiladze U, Kirtadze N, Giorgadze M, Amashukeli N, Parulava N, Iluridze N, Kikabidze N, Gudavadze N, Gelashvili L, Koberidze V, Gigashvili E, Jajanidze N, Latsabidze N, Mamageishvili N, Shengelia R, Hovhannisyan A, Panossian A. Efficacy of Adaptogens in Patients with Long COVID-19: A Randomized, Quadruple-Blind, Placebo-Controlled Trial. Pharmaceuticals (Basel). 2022 Mar 11;15(3):345. doi: 10.3390/ph15030345. PMID: 35337143; PMCID: PMC8953947. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8953947/ (Full text)