Clinical Effect of Fuyang Prescription in Treatment of Ischemic Stroke during the Convalescent Stage: An Analysis of 25 Cases

Menghua WEI, Xiaoping MEI, Xueni MO, Kaihua WANG, Ying CHEN, Min ZOU, Jianlong SHU, Yang ZHAI,*

1. Wei’s Traditional Chinese Medicine Clinic, Baise 542899, China; 2. Guangxi International Zhuang Medicine Hospital, Nanning 530023, China; 3. Guangxi University of Chinese Medicine, Nanning 530001, China

Abstract [Objectives] The paper was to investigate the clinical effect of Fuyang prescription in the treatment of yang deficiency syndrome in the convalescent stage of ischemic stroke (IS) and its mechanism of action. [Methods] A total of 50 patients with yang deficiency syndrome in the convalescent stage of IS were randomly divided into treatment group and control group, with 25 patients in each group. The patients in the treatment group were given basic treatment combined with Fuyang prescription, and those in the control group were given basic treatment combined with Buyang Huanwu decoction; the course of treatment was 28 d for both groups. The activities of daily living (ADL) score, National Institutes of Health Stroke Scale (NIHSS) score, quality of life score, TCM syndrome score, and safety in both groups were observed before treatment and at 14 and 28 d post treatment, and their clinical outcome was evaluated. [Results] There was a significant difference in overall response rate between the treatment group and the control group[92.00% (23/25) vs 76.00% (19/25), P<0.05]. After treatment, both groups had significant changes in ADL score, NIHSS score, quality of life score, and TCM syndrome score, and there were significant differences in these indices between the two groups at the same time point after treatment (P<0.05 or P<0.01). There were no significant changes in routine blood, routine stool, routine urine, and liver/renal function in either group after treatment. [Conclusions] Fuyang prescription has a marked clinical effect in the treatment of yang deficiency syndrome in the convalescent stage of IS, with significantly better clinical effect than Buyang Huanwu decoction, and it provides clinical evidence for the traditional Chinese medicine theory of yang supporting in the treatment of IS in the convalescent stage.

Key words Convalescent stage of ischemic stroke, Fuyang prescription, Buyang Huanwu decoction

1 Introduction

Stroke is the leading cause of death and disability in the global population, and about 85% of stroke cases are caused by ischemic stroke (IS)[1]. In China, 24 out of 10 000 people suffer from stroke every day, with a fatality rate of 24.68%. The incidence of stroke in rural residents is significantly higher than that in urban residents, while the burden of disease caused by stroke is also increasing year by year, and the treatment cost is constantly rising[2]. Therefore, it has become a hot spot in the current study of stroke by finding more effective prevention and control measures to reduce the incidence and mortality and to improve the prognosis. Traditional Chinese medicine (TCM) can improve the quality of life of IS patients. TCM compounds play an important role in clinical treatment due to the advantages of small toxic and side effects, multiple targets and low treatment cost[3]. Yang deficiency is the root cause of stroke. Based on this, the study used self-designed Fuyang prescription to treat 25 patients in convalescent stage of IS caused by deficient and weak yang qi common in clinical practice, and achieved satisfactory curative effect.

2 Clinical data

2.1 General dataA total of 50 patients with yang deficiency syndrome in the convalescent stage of IS hospitalized in the Department of Encephalopathy, Guangxi International Zhuang Medical Hospital from March 2020 to March 2021 were selected and divided into treatment group and control group by random number table method, with 25 patients in each group. In the treatment group, there were 14 males and 11 females aged from 41 to 75 years, with an average age of (54.43±8.55) years. In the control group, there were 16 males and 9 females aged from 41 to 75 years, with an average age of (53.62±8.94) years. There was no significant difference in the general data between the two groups (P>0.05). This study was approved by the Ethics Committee of Guangxi International Zhuang Medical Hospital (LS[2020]029-01).

2.2 Diagnostic criteria

2.2.1Diagnostic criteria for IS. It was formulated according to the relevant standards in theChineseGuidelinesfortheDiagnosisandTreatmentofCerebralInfarctionbyIntegratedTraditionalChineseandWesternMedicine(2017)[4]. (i) Main symptoms: hemiplegia, deviation of mouth and tongue, muddle-headed consciousness, dysphasia or in silence, hemianesthesia; (ii) Sudden onset; (iii) There are many causes of illness, and often premonitory symptoms before the onset. With more than 2 main symptoms and sudden onset, it can be diagnosed combined with inducement, aura, age and so on.

2.2.2Differentiation criteria for yang deficiency syndrome. It was drawn up according toPracticalChineseMedicineInternalMedicine[5]andAComparativeStudyoftheChapteronTraditionalMedicineinthe11thRevisionoftheInternationalClassificationofDiseases(ICD-11)andtheNewNationalStandardofTraditionalChineseMedicine[6]. (i) Main symptoms: systemic or local chills or cold limbs, floating face and foot; (ii) Secondary symptoms: frequent night urination with clear urine, loose stool; (iii) Tongue and pulse: The tongue is light and fat, with moist moss and slightly delayed pulse. With at least 1 main symptom (item 1 required) and 1 secondary symptom, it can be clearly differentiated combined with tongue and pulse.

2.3 Inclusion criteria(i) The symptom meets the above criteria of western medicine diagnosis and TCM syndrome differentiation; (ii) The patients are 18-80 years old; (iii) The course of the disease is 2-4 weeks; (iv) The patient is conscious; (v) The patient agrees to accept the study and signs the informed consent form.

2.4 Exclusion criteria(i) The patient suffers from serious cardiopulmonary diseases and major immune diseases; (ii) The patient with psychosis and deaf-mute with a history of dementia; (iii) The patient has accepted other clinical trials.

3 Therapeutic method

3.1 Basic treatmentThe patient was given routine western medicine treatment. Aspirin Enteric-coated Tablets (Bayer Vital GmbH, approval number H20130340, specification 100 mg/tablet) were taken orally once a day, 1 tablet/time; Atorvastatin Calcium Tablets (Lek Pharmaceuticals d. d, approval number Sinopharm H20130581, specification 20 mg/tablet) were taken orally once a day, 1 tablet/time.

3.2 Treatment groupOn the basis of basic treatment, the patient was treated with Fuyang prescription. Fuyang prescription is composed of 15 g of Radix Aconitilateralis Preparata, 15 g of Radix Astragali, 15 g of Radix Codonopsis, 15 g of Herba Epimedii, 15 g of Radix Notoginseng, 15 g of Rhizoma Acori Tatarinowii, 10 g of Rhizoma Zingiberis, and 6 g of Radix Glycyrrhizae Preparata.

3.3 Control groupOn the basis of basic treatment, the patient was treated with Buyang Huanwu decoction. Buyang Huanwu decoction is composed of 60 g of Radix Astragali, 15 g of Persicae Semen, 10 g of Flos Carthami, 15 g of lumbricus, 15 g of Radix Paeoniae Rubra, 15 g of Radix Angelicae Sinensis, and 15 g of Rhizoma Chuanxiong.

4 Observation of curative effect

4.1 Observation index

4.1.1Activities of daily living (ADL) score. ADL scale was used for evaluation before treatment, at 14 and 28 d post treatment. There are 10 items in the ADL score, each of which is 10 points, with a full score of 100. The higher the score, the greater the independence and the smaller the dependence of the patient[7].

4.1.2Neurological score. The National Institutes of Health Stroke Scale (NIHSS) was used for evaluation before treatment, at 14 and 28 d post treatment. 0 point indicates normal neurological function; 1 point indicates near-normal neurological function; 2-4 points indicate mild stroke; 5-14 points indicate moderate stroke; 15-20 points indicate moderate to severe stroke; 21-42 points indicate severe stroke. The lower the score, the better the patient’s neurological function[8].

4.1.3Quality of life score. The quality of life scale was used for evaluation before treatment, at 14 and 28 d post treatment. The scale included independent eating, bathing, dressing, going to the toilet, walking, defecation and urination, which were counted as 10, 5 and 2.5 and 0 points according to independence, little dependence, moderate dependence and complete dependence, respectively. The higher the score, the better the quality of life[9].

4.1.4TCM syndrome score. According to relevant standards inGuidingPrinciplesforClinicalResearchofNewChineseMedicine, the TCM syndrome was evaluated before treatment, at 14 and 28 d post treatment[10]. The symptoms of hemiplegia, deviation of mouth and tongue, muddle-headed consciousness, dysphasia or in silence were counted as 2, 4 and 6 points according to mild, moderate and severe incidence; the symptoms of intolerance of cold and cold limbs, floating face and foot, and stiff limbs were counted as 1, 2 and 3 points according to mild, moderate and severe incidence; the score was 1 and 0 according to the presence or absence of light and fat tongue, moist moss, and slightly delayed pulse. The higher the score, the more severe the symptoms.

4.1.5Security index. Blood routine, stool routine, urine routine and liver/renal function were detected before and after treatment.

4.2 Criterion of therapeutical effectThe criterion of therapeutical effect was formulated according to relevant standards inGuidingPrinciplesforClinicalResearchofNewChineseMedicine[10]. Reduction rate of TCM syndrome score=(Score before treatment - Score after treatment)/ Score before treatment×100%. Clinical recovery: The clinical symptoms and signs disappeared or basically disappeared, reduction rate of TCM syndrome score≥95%; Marked response: The clinical symptoms and signs were significantly improved, 70%≤reduction rate of TCM syndrome score<95%; Moderate response: The clinical symptoms and signs were improved, 30%≤reduction rate of TCM syndrome score<70%; No response: The clinical symptoms and signs were not significantly improved, or even aggravated, reduction rate of TCM syndrome score<30%.

4.4 Therapeutic outcome

4.4.1Comparison of clinical efficacy between the two groups. The total response rate was 92.00% in the treatment group and 76.00% in the control group, and the difference was statistically significant (P<0.05, Table 1).

Table 1 Comparison of clinical efficacy between the two groups [n=25, (case/%)]

4.4.2Comparison of ADL score, NIHSS score, quality of life score and TCM syndrome score between the two groups before treatment, at 14 and 28 d post treatment. There were significant differences in ADL score, NIHSS score, quality of life score and TCM syndrome score between the two groups at 14 and 28 d post treatment compared with those before treatment (P<0.05 orP<0.01). There were statistically significant differences between the treatment group and the control group 14 and 28 d post treatment (P<0.05, Table 2).

Table 2 Comparison of ADL score, NIHSS score, quality of life score and TCM syndrome score between the two groups before treatment, at 14 and 28 d post treatment(n=25, point)

4.4.3Comparison of security between the two groups. There were no significant changes in blood routine, stool routine, urine routine and liver/renal function in the two groups before and after treatment.

5 Discussion

At present, the understanding of the pathogenesis of IS in traditional Chinese medicine has not been completely unified. Supporting Yang School has its unique and profound understanding on the fundamental understanding of yang deficiency as the pathogenesis of stroke, which has been put into clinical practice for more than 100 years with outstanding curative effect and formed a systematic and perfect treatment system. Based on previous literature and clinical studies, our research group believed that yang deficiency is the root cause of stroke[11], that is, "yang deficiency is the foundation". Yang qi should be in the core of the human body, that is, yang is centered inside, while yin is naturally centered outside. This is the ontology structure of human yin and yang[12]. Yin and yang are not solid, but dynamic. In the "use" level, yang moves outward, while yin moves inward. Whether the human body is sick or not has a great deal to do with whether yin and yang deviate from their original position in static and movement state, which is the essence of "the equilibrium of yin and yang makes the vitality well-conserved". However, on the theoretical basis of "yang transforming qi while yin constituting form", because of the problems of yin and yang at the level of "use", the movement and qi transformation is obstructed and the sympathetic harmony can not be achieved. It is suggested that there are two aspects that become the etiology and pathogenesis of IS at the level of yin and yang. The first is too abundant yin qi, which becomes a tangible thing blocking blood vessels. The second is dysfunction of yang qi in transformation; in the case of normal yin qi, yang qi can not transform yin cold and constitute form, leading to stroke. Finally, yin cold is inside and yang qi is blocked in the periphery, making it a state of "yang outside and yin inside". After the basic movement disorder of yin and yang, the phlegm, toxin and blood stasis are blocked in brain orifice through the effect of internal injury and six exogenous pathogenic factors, causing dizziness and paralysis of the body, and the disease of stroke. Based on the above theories, our research group believed that IS essentially is a "triple-yin disease" in traditional Chinese medicine, which should be treated by strengthening yang qi. As Mr. Zheng Qin’an put forward in the Qing Dynasty that "all triple-yin diseases should be treated with warm tonification", when Yuanyang is healthy, the disease will be cure. Under the guidance of the theory of strengthening yang qi, Jiawei Sini decoction is designed for this symptom. The bias is corrected through the function of Jiawei Sini decoction, making primordial yang return to the standard. Fuyang prescription is composed of Radix Aconitilateralis Preparata, Radix Astragali, Radix Codonopsis, Herba Epimedii, Radix Notoginseng, Rhizoma Acori Tatarinowii, Rhizoma Zingiberis, and Radix Glycyrrhizae Preparata. It is derived from the Sini decoction in theTreatiseonFebrileandMiscellaneousDiseases, and integrates the essence of the theory of strengthening yang qi in traditional Chinese medicine, aiming at yang deficiency as the fundamental cause of IS. In the prescription, Radix Aconitilateralis Preparata can recover yang qi in the body, and warm the life-gate fire, being the main drug of reviving the yang for resuscitation. Radix Astragali and Radix Codonopsis replenish qi and blood. In the process of reviving the yang for resuscitation, they supplement human qi and blood, resulting in sufficient qi and blood, and have the power of supporting yang. Herba Epimedii is mildly warm, which introduces the yang of Radix Aconitilateralis Preparata into yin and helps the intercourse of yin and yang. Radix Notoginseng is bitter and warm, and it introduces drugs upward, removes the stagnation in qi movement and coagulation in blood, and breaks coagulation in intima, being an adjuvant. The combined use of Rhizoma Zingiberis, Radix Aconitilateralis Preparata, Herba Epimedii and Rhizoma Acori Tatarinowii will eliminate blood stasis and turbid yin in the brain along with the movement of yang qi, so that qi and blood run smoothly in the body and the meridian vessels are soft. The combined use of Radix Glycyrrhizae Preparata and Rhizoma Zingiberis make the fire descend into life-gate, preventing the syndrome of flaring up of deficient fire. Meantime, it reconciles the strong nature of Radix Aconitilateralis Preparata, and warms the spleen yang in the middle energizer and the kidney yang in the lower energizer. Throughout the whole prescription, the drugs are simple, but specifically play the role of breaking yin and restoring yang to restore the ontology structure of internal yang and external yin, and smooth movement of yin and yang, making blood stasis and turbid yin have no chance to retain.

The research results showed that in terms of curative effect on patients with yang deficiency syndrome in the convalescent stage of IS, the total response rate of the treatment group was significantly higher than that of the control group, and the ADL score, NIHSS score, quality of life score and TCM syndrome score in treatment group were better than those in the control group. The results suggest that warming yang therapy is an important treatment in the convalescent stage of IS, It is suitable for the pathogenesis of stroke based on yang deficiency and provides a new idea for clinical treatment of the disease.