Efficacy and safety of aniseed powder for treating gastrointestinal symptoms of COVID-19: a randomized, placebo-controlled trial.

Background: Gastrointestinal symptoms are prevalent amongst patients with a confirmed diagnosis of COVID-19 and may be associated with an increased risk of disease severity. This trial aimed to evaluate the efficacy and safety of aniseed (Pimpinella anisum L.) powder as an add-on therapy to standard care for treating gastrointestinal symptoms experienced by adults with an acute SARS-CoV-2 infection. Methods: The study was a randomized parallel-group double-blinded placebo-controlled add-on therapy trial. Adults with an acute SARS-CoV-2 infection who did not require hospitalization and reported at least one gastrointestinal symptom in the preceding 48 h were assigned to either the aniseed or placebo group in a 1:4 ratio. All 225 participants (45 in the aniseed group and 180 in the placebo group) were instructed to use 25 g of powdered aniseed or placebo twice daily for 2 weeks. The primary outcomes were the proportion of patients who experienced an improvement of at least one point in the symptom score after adjusting for age group, gender, and time. Backwards stepwise logistic regression was applied to calculate the risk ratios. The clinical symptoms and adverse events were assessed at the beginning, 1 week later, and at the end of the trial (week two). Results: Participants in the aniseed group were significantly more likely to report symptom improvement for abdominal pain [adjusted risk ratio (RR):0.55; 95% confidence interval (CI): 0.46-0.72], anorexia (RR:0.62; 95% CI: 0.47-0.82), and diarrhea (RR:0.19; 95% CI: 0.12-0.30), but not nausea/vomiting (RR:0.87; 95% CI: 0.71-1.08) or bloating (RR:0.87; 95% CI: 0.72-1.05). Two participants in the aniseed group and three participants in the placebo group reported mild to moderate adverse events. Conclusion: This study showed that 2 weeks of aniseed powder containing trans-anethole (87%-94%) may help improve abdominal pain, anorexia, and diarrhea in COVID-19 patients. The findings align with the known biological, multitargeted activity of P. anisum and trans-anethole, which includes inhibiting SARS-CoV-2 along with other anti-infective, anti-inflammatory, antioxidant, hepatoprotective, and anti-dysbiosis properties. Multicenter trials with larger sample sizes and longer follow-up are warranted to confirm these findings. Clinical Trial Registration: Iranian Registry of Clinical Trials (IRCT20120506009651N3).

Efficacy and safety of purslane (Portulaca oleracea) for mild to moderate chronic hand eczema; A randomized, double-blind, placebo-controlled clinical trial.

INTRODUCTION: Chronic hand eczema (CHE) is a common skin inflammation with a complex pathophysiology. Due to its anti-inflammatory properties, Portulaca oleracea L. (purslane) is traditionally used in Persian medicine for skin ailments. This study aimed to evaluate the safety and efficacy of a standardized purslane extract (based on traditional Persian medicine) for adults with mild or moderately severe CHE. METHODS: A randomized, double-blind, placebo-controlled clinical trial was conducted at Razi Hospital in Iran from January to June 2022. Participants were randomly allocated to receive an oral purslane or placebo syrup plus topical Vaseline for four weeks. Seventy participants were randomly allocated into the intervention (n = 35) and placebo (n = 35) groups. The primary outcomes were the extent and severity of CHE symptoms over the four weeks after adjusting for age, gender and baseline score. Secondary outcomes were quality of life, symptom recurrence, treatment satisfaction, and adverse events. RESULTS: After 4 weeks of treatment, compared to the placebo group (n = 31), the purslane group (n = 31) had significantly lower physician-reported fissure scores (adjusted mean difference (adjMD): -0.50, 95 %CI -3.93 to -0.34, p = 0.043), participant-reported itching (adjMD -0.51, 95 %CI -2.32 to -0.31, p = 0.041), dryness (adjMD -1.46, 95 %CI -2.89 to -0.03, p = 0.045), and total itching, dryness and thickness (adjMD -2.36, 95 %CI -6.23 to -1.51, p = 0.023) scores. Fourteen participants (purslane n = 10; placebo n = 4, p = 0.068) experienced adverse events of mild to moderate severity. CONCLUSION: Purslane has some promising effects for reducing the extent and severity of CHE symptoms, and no direct comparisons have been made with commonly used treatments. Future multicenter trials and mechanistic studies are warranted to establish the safety and effectiveness of purslane as a potential therapeutic agent for CHE. TRIAL REGISTRATION: Iranian Registry of Clinical Trials (IRCT20200707048040N1).

Targeting autophagy with natural products to prevent SARS-CoV-2 infection.

Autophagy is a catabolic process that maintains internal homeostasis and energy balance through the lysosomal degradation of redundant or damaged cellular components. During virus infection, autophagy is triggered both in parenchymal and in immune cells with different finalistic objectives: in parenchymal cells, the goal is to destroy the virion particle while in macrophages and dendritic cells the goal is to expose virion-derived fragments for priming the lymphocytes and initiate the immune response. However, some viruses have developed a strategy to subvert the autophagy machinery to escape the destructive destiny and instead exploit it for virion assembly and exocytosis. Coronaviruses (like SARS-CoV-2) possess such ability. The autophagy process requires a set of proteins that constitute the core machinery and is controlled by several signaling pathways. Here, we report on natural products capable of interfering with SARS-CoV-2 cellular infection and replication through their action on autophagy. The present study provides support to the use of such natural products as adjuvant therapeutics for the management of COVID-19 pandemic to prevent the virus infection and replication, and so mitigating the progression of the disease.

An overview of the anti-SARS-CoV-2 properties of Artemisia annua, its antiviral action, protein-associated mechanisms, and repurposing for COVID-19 treatment.

Artemisia annua and its phytocompounds have a rich history in the research and treatment of malaria, rheumatoid arthritis, systemic lupus erythematosus, and other diseases. Currently, the World Health Organization recommends artemisinin-based combination therapy as the first-line treatment for multi-drug-resistant malaria. Due to the various research articles on the use of antimalarial drugs to treat coronaviruses, a question is raised: would A. annua and its compounds provide anti-severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) properties? PubMed/MEDLINE, Scopus, and Google Scholar were searched for peer-reviewed articles that investigated the antiviral effects and mechanisms of A. annua and its phytochemicals against SARS-CoVs. Particularly, articles that evidenced the herb's role in inhibiting the coronavirus-host proteins were favored. Nineteen studies were retrieved. From these, fourteen in silico molecular docking studies demonstrated potential inhibitory properties of artemisinins against coronavirus-host proteins including 3CLPRO, S protein, N protein, E protein, cathepsin-L, helicase protein, nonstructural protein 3 (nsp3), nsp10, nsp14, nsp15, and glucose-regulated protein 78 receptor. Collectively, A. annua constituents may impede the SARS-CoV-2 attachment, membrane fusion, internalization into the host cells, and hinder the viral replication and transcription process. This is the first comprehensive overview of the application of compounds from A. annua against SARS-CoV-2/coronavirus disease 2019 (COVID-19) describing all target proteins. A. annua's biological properties, the signaling pathways implicated in the COVID-19, and the advantages and disadvantages for repurposing A. annua compounds are discussed. The combination of A. annua's biological properties, action on different signaling pathways and target proteins, and a multi-drug combined-therapy approach may synergistically inhibit SARS-CoV-2 and assist in the COVID-19 treatment. Also, A. annua may modulate the host immune response to better fight the infection.

The "Treatise on the spleen and stomach" (Pí Wèi Lùn) as the first record of multiple sclerosis in the medical literature - A hypothesis based on the analysis of clinical presentation and herbal medicine.

BACKGROUND: The "Treatise on the spleen and stomach" (Pí Wèi Lùn) is the work of the scholar and physician Li Gao (Jin-Yuan dynasties, 1115-1368 C.E., China). Li Gao described a clinical presentation that today would fall under the diagnosis of Multiple Sclerosis (MS) and proposed the treatment with herbal medicine and nutritional guidelines. The PWL is well known for its application in the treatment of MS and autoimmune conditions. However, this theoretical "MS" has not yet been analyzed through a scientific investigation, and research on its herbal formulations for MS is scant. METHODS: We analyzed the PWL "MS" clinical presentation considering biomedical diagnostic criteria and neurological correlates. To support our review, we searched Pubmed for studies on the PWL main herbal formulas and their herbs/isolates used for the believed "MS" which treated experimental autoimmune encephalomyelitis (EAE)/MS. RESULTS: We found a very close correlation between the PWL "MS" and the current MS diagnosis. Twenty four studies on the herbs-isolates showed significant amelioration of EAE, neuronal damage, and demyelination. DISCUSSION: Collectively, Astragali radix, Ginseng radix, Glycyrrhizae radix, and berberine containing Phellodendri cortex reduced the severity of EAE through different signaling pathways and mechanisms of action. These herbs provided a wide range of properties such as anti-inflammatory, anti-oxidant, anti-microglial activation, anti-infiltration of leukocytes, apoptotic/anti-apoptotic balance, and neuronal protection. CONCLUSION: Our review proposes that the PWL is the first record of MS in the medical literature. Its formulas and herbs-isolates offer a fertile area for MS research and an invaluable potential for its treatment.

The antiviral and coronavirus-host protein pathways inhibiting properties of herbs and natural compounds - Additional weapons in the fight against the COVID-19 pandemic?

INTRODUCTION: As of March 11th, 2020, the World Health Organization declared the COVID-19 outbreak a pandemic. Articles published after the SARS-CoV-1 (2002) epidemic suggest that the use of an herbal-drug integrative medical approach could have contributed to a lower fatality rate and a more rapid response in controlling the outbreak. METHODS: Pubmed was searched for articles that investigated the antiviral properties and mechanisms of action of herbs or natural compounds against the SARS-coronavirus (CoV). RESULTS: Forty-three (43) relevant papers were located. A general count rendered 450+ herbs and natural compounds with antiviral properties against the SARS-CoV and related viruses. From the 43 articles, thirty-one (31) uncovered the mechanisms of action of the natural substances able to oppose the coronavirus. DISCUSSION: A series of herbs and natural compounds demonstrated moderate to strong antiviral activity. Research on many herbs-natural compounds also showed potent and significant inhibition of CoV-host protein pathways responsible for different phases of viral replication specifically targeting 3CLPRO, PLPRO, RdRp, helicase protein, S protein, N protein, 3a protein, Cathepsin L, Nsp1, Nsp3c, and ORF7a, and the S protein/ACE-2 interaction. CONCLUSION: The herbs-natural compounds with antiviral activity and that caused inhibition/blockade of the CoV-host protein pathways are potential therapeutic candidates. The homology between the SARS-CoV-1 and SARS-CoV-2 is around 80%. Thus, effective herbs-compounds for the former would likely be beneficial for the latter also depending on target protein similarities between the viruses. Here we provide the mechanistic bases supporting an integrative approach that includes natural compounds to fight coronavirus infections.