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Thursday, 5 March 2020

Systematic Review of Modified Yupingfeng San and its Potential Effects on Covid 19

Tiejun Tang

Yupingfeng San (YPF) is the most commonly used formula for prevent disease in the history of traditional Chinese medicine. It consists of three ingredients. They are Huangqi (Astmgali Radix), Baizhu ( Largehead Atractylodes Rh) and Fangfeng (Divaricate Saposhniovia Root.). It has been widely used in China since the Yuan dynasty (1217 AD). According to traditional Chinese medicine philosophy, this formula can build up healthy Qi and to prevent invasion of external evils. In Chinese “Yupingfeng mean jade screen and San mean powder. Is it possible to use YPF to prevent and treat Covid 19? Is there any scientific research evidence to support the clinical application of this classical formula? This paper aimed to answer these questions by systematic review.

Methods

Database includes PubMed, MEDLINE, CNKI, CSCD. Use Yupingfeng as key word.

Search time limit is from 2000-2020. All the Included articles were published in English.

Results

1.    Immunoregulatory and anti-inflammatory function

Inflammatory cytokine storm is very important pathological change of Covid 19.

To observe the Immunoregulatory and anti-inflammatory effects of YPF, Song J. applied YPF to treat a rat chronic bronchitis model. The results showed that the inflammation in the pulmonary tissue and the bronchus of rats was significantly reduced in the treatment groups.  In serum samples collected at different times from rats after administration of YPF, the result showed increased proliferation of splenic lymphocytes area. They use serum samples of YPF group to treat alveolar macrophages. The result found interleukin-8 (IL-8) in the cell culture media has been inhibited [1].

IL-8 plays an important role in the pathogenesis of bronchitis and cystic fibrosis. It also is a very important pathological factor in the cytokine storm of Covid 19 [2]. To investigate the immunomodulating mechanism of YPF, Sun H applied YPF polysaccharides to treat mice lymphocytes and macrophages. The results showed YPF polysaccharides effectively enhanced the proliferation of lymphocytes and promoted mRNA expression of inducible nitric oxide synthase (iNOS), IL-6, TNF-α, INF-γ, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and TLR-4 in lymphocytes and macrophages. Moreover, it can effectively normalized cell proliferation and down regulated mRNA expression levels of pro-inflammatory cytokines, NF-κB, TLR-4, and iNOs in chronic inflammation cells [3]. These cytokine factors all play important role in the chain reaction of Covid 19 cytokine storm [2].

2.    Anti-virus effect function

Coronavirus is the pathogen of Covid 19. The anti-virus effect of YPF was approved by some laboratory researches. To investigate the antivirus effect of YPF, Liu Q. applied real-time RT-PCR and western blotting technique to detect influenza virus (IFV) and the human respiratory syncytial virus (HRSV). The result showed YPF extract inhibited both IFV and HRSV in a dose-dependent manner when given before, during and after a viral infection. YPF was effective in blocking the entry of the virus. Furthermore, pre-treatment with YPF reduced the susceptibility of cells to the invasion of HRSV by inhibiting the expression of ICAM-1. YPF extract increased the survival rate of lethal influenza-infected mice, prolonged the survival time and alleviated the virus-induced lung lesions, which is comparable with the effects of ribavirin treatment [4]. To enhance the anti coronavirus function of YPF, I added Lizhihe (Litchi core) in my modified YPF formula, because of it can significantly inhibit protease activity of SARS coronavirus 3CL [5].

3.    Anti-asthma function

Difficulty breathing is one of the common symptoms of Covid 19. Previous studies showed YPF has a good function of anti-asthma.  Wang Z. reported that YPF could alleviate the inflammation in the lung tissue of mice, decrease the proportion of Th17 cells, and increase the proportion of Treg cells in bronchoalveolar lavage fluid, it could decrease IL-4 and TNF-α level and increase TGF-β level in blood [6]. Liu X applied network pharmacology to explore potential mechanism of YPF on asthma. In vitro experiments showed that YPF significantly decreased the production of TNF-α and IL-6, as well as both mRNA and protein levels of IL-1β, NLRP3, Caspase-1 and ASC. In vivo experiment showed YPF treatment not only reduce the clinical symptoms, but also reduced inflammatory cell infiltration, mucus secretion in lung of asthmatic mice. Moreover, YPF treatment remarkably decreased the mRNA and protein levels of IL-1β, NLRP3, Caspase-1 and ASC in lung of asthmatic mice [7].

4.    Anti pulmonary fibrosis

Pulmonary fibrosis is a major pathological change in Covid 19 patients. YPF showed an anti pulmonary fibrosis function in the previous studies. Li L applied total extract of YPF to treat bleomycin-induced pulmonary fibrosis in rats. The result showed YPF treatment can reduce the alveolitis and fibrosis, reduced the loss of body weight and increase of lung coefficient. YPF also significantly decreased the levels of hydroxyproline and type I collagen, and reduced the over-expression of high-mobility group box 1 (HMGB1), transforming growth factor-beta 1 (TGF-β1), Col-I and α-smooth muscle actin (α-SMA) .It can improve lung fibrosis by alleviating HMGB1 activity and TGF-β1 activation [8].

Cui W applied the total glycoside of Yupingfeng (YPF-G) to treat pulmonary fibrosis, the result found that both dose of YPF-G significantly reduced bleomycin-induced alveolitis and pulmonary fibrosis in rats. The levels of HMGB1, laminin, hyaluronic acid, and hydroxyproline were effectively reduced. The increased protein expression of HMGB1 was dramatically inhibited after YPF-G treatment [9].

5.    Clinical randomized controlled trials

Except laboratory research YPF also showed some good effects on clinical trials of some related diseases include SARS. A meta-analysis aimed to evaluate the immunomodulating function of YPF in children with recurrent respiratory tract infections. Twelve trials with 1236 patients were identified. YPF significantly increased serum levels of IgA, IgG, IgM and CD3 (+) T-lymphocytes. It also reduced the frequency of recurrent respiratory tract infections and increased total effective rates of symptom improvement [10]. A randomized, double-blind, parallel, placebo-controlled study analysed 240 patients from eight centres in China. Participants were eligible if they had mild to severe chronic obstructive pulmonary disease. They were randomly assigned to receive YPF or placebo. The result showed YPF group had a significantly lower exacerbation rate than placebo group and a significantly reduced risk of second exacerbation. The mean change in the COPD assessment test score in the YPF group were signifacantly lower than placebo group [11].

During the epidemic period of SARS in Hong Kong there were 2,601 medical staff administered with Kandu Bufei  Decoction which is a modified YPF It was confirmed that 1,063 people had taken it for a successive two weeks. They were regarded as the treatment groupThe control group consisted of 15,374 subjects who didn’t take Chinese herbal medicineThe result showed: No one in the herbal treatment group contracted the SARS infection while in the control group, 64(0.4%) were infected [12].

Discussion

The pandemic of Covid 19 is gradually getting under control in China. Chinese herbal medicine played a very important role in this battle against Covid 19 in China. More than 85% of patients received herbal medicine treatment. Because the involvement of Chinese herbal medicine the cure rate was significantly increased and mortality rate significantly decreased.

YPF is a natural immune enhancer. Its immunoregulatory function can prevent viral infection. The anti-inflammatory and antivirus function can block the cytokine storm reaction of Covid 19. The anti-asthma effect can release the shortness of breath. The anti pulmonary fibrosis effect can reduce the pulmonary fibrosis in the severe stages and recover stages.

Conclusions

Based on above research evidence we have reason to conclude YPF probably has the effects on prevention and treatment of Covid 19.

Reference

  1.  Song J. Anti-inflammatory and immunoregulatory effects of Yupingfeng powder on chronic bronchitis rats. Chin J Integr Med. 2013; 19(5):353-9.
  2.  Xuetao Cao. COVID-19: immunopathology and its implications for therapy. Nature Reviews Immunology . 2020; 20, 269-270.
  3.  Sun H. Bidirectional immunomodulating activity of fermented polysaccharides from Yupingfeng. Res Vet Sci. 2017; 110:22-28.
  4.  Liu Q. Jiawei-Yupingfeng-Tang, a Chinese herbal formula, inhibits respiratory viral infections in vitro and in vivo. J Ethnopharmacol. 2013; 150 (2):521-8.
  5. Shouji Gong.  A study on anti-SARS. CoV 3CL protein of flavonoids from litchichinem  sonn core. Chinese Pharmacological Bulletin 200824 (5): 699700.
  6. Wang Z. Yupingfeng Pulvis Regulates the Balance of T Cell Subsets in Asthma Mice. Evid Based Complement Alternat Med. 2016; 6916353.
  7.  Liu X. Yupingfeng San Inhibits NLRP3 Inflammasome to Attenuate the Inflammatory Response in Asthma Mice. Front Pharmacol. 2017; 8, 1-12.
  8.   Li L. Total extract of Yupingfeng attenuates bleomycin-induced pulmonary fibrosis in rats.Phytomedicine. 2015; 22 (1):111-9.
  9.  Cui W. Total glycosides of Yupingfeng protects against bleomycin-induced pulmonary fibrosis in rats associated with reduced high mobility group box 1 activation and epithelial-mesenchymal transition.Inflamm Res. 2015; 64(12):953-61.
  10. Song T. Adjuvant Treatment with Yupingfeng Formula for Recurrent Respiratory Tract Infections in Children: A Meta-analysis of Randomized Controlled Trials.Phytother Res. 2016; 30 (7):1095-103.
  11.  Ma J. Effects of YuPingFeng granules on acute exacerbations of COPD: a randomized, placebo-controlled study.Int J Chron Obstruct Pulmon Dis. 2018; 13, 3107-3114.
  12. Liu Dehui. Clinical Observation on the Preventive Effect of KangduBufei Decoction on AcuteSevere Respiratory Syndrome. Chinese Journal of Integrated Traditional and Western Medicine. 2004; 24(8): 685-688.