Submitted Successfully!
To reward your contribution, here is a gift for you: A free trial for our video production service.
Thank you for your contribution! You can also upload a video entry or images related to this topic.
Version Summary Created by Modification Content Size Created at Operation
1
Guangzheng Xu
 + 1536 word(s) 1536 2021-11-14 10:15:16 |
2 Format correct
Vicky Zhou
 Meta information modification 1536 2021-12-21 01:41:19 |

Video Upload Options

Do you have a full video?
Send video materials Upload full video

Confirm

Are you sure to Delete?
Yes No
Cite
If you have any further questions, please contact Encyclopedia Editorial Office.
Xu, G. Xiaochaihu. Encyclopedia. Available online: https://encyclopedia.pub/entry/17345 (accessed on 19 May 2024).
Xu G. Xiaochaihu. Encyclopedia. Available at: https://encyclopedia.pub/entry/17345. Accessed May 19, 2024.
Xu, Guangzheng. "Xiaochaihu" Encyclopedia, https://encyclopedia.pub/entry/17345 (accessed May 19, 2024).
Xu, G. (2021, December 20). Xiaochaihu. In Encyclopedia. https://encyclopedia.pub/entry/17345
Xu, Guangzheng. "Xiaochaihu." Encyclopedia. Web. 20 December, 2021.
Xiaochaihu
Edit
This entry is adapted from the peer-reviewed paper 10.3390/separations8110199

Xiaochaihu (XCH) is a classic Chinese medicine formula. XCH tablet, XCH granule, XCH capsule, and XCH effervescent tablet are included in the Chinese Pharmacopoeia. 

Xiaochaihu (XCH) formula preparations quality control standard

1. Introduction to XCH Formula

Xiaochaihu (XCH) formula, which was created by Zhang Zhongjing in the East Han Dynasty, is capable of inducing sweat to dispel heat, channeling the liver, regulating the spleen, soothing the stomach [1], etc. Traditionally, the recipe is composed of Bupleuri Radix , Scutellariae Radix , Ginseng Radix Et Rhizoma ( Ginseng Radix ), Glycyrrhizae Radix Et Rhizoma Praeparata Cum Melle ( Glycyrrhizae Radix ), Zingiberis Rhizoma Recens , Jujubae Fructus , and Pinelliae Rhizoma [2]. According to the principle of JUN-CHEN-ZUO-SHI (emperor-minister-assistant-courier in English), in this formula, Bupleuri Radix is JUN, Scutellariae Radix is CHEN, Glycyrrhizae Radix is SHI, and the others are ZUO. Modern research has verified that XCH has anti-inflammatory [3] and antitumor [4] functions and regulates the endocrine system [5]. Clinically, the formula is applied to treat various diseases of the respiratory system [6], digestive system [7], urogenital system [8], immune system [9], circulatory system [10], etc. The mechanism of XCH acting on the human body can be preliminarily explored by means of liquid chromatography-mass spectrometry, network pharmacology, and animal experiments. For fever, the widest application of XCH, potential antipyretic mechanism includes the reduction of inflammation level, inhibition of endogenous pyrogen and COX-2 [11]. Some active ingredients of XCH including quercetin, baicalein, and hanbaicalein can significantly inhibit the growth of hepatocellular carcinoma and induce apoptosis of hepatocellular carcinoma cells [12]. In recent years, many novel applications have been reported, including the prevention and treatment of methicillin-resistant Staphylococcus aureus [13], syncytial virus, and adenovirus [14], as well as the inhibition of influenza A virus [15], etc. For the period from 2000 to 2020, an overall trend of a steady rise in the numbers of publications in the field of XCH could be found. In the database of www.cnki.net , the number has grown annually and ranged from about 150 to nearly 400 works [16].

2. Formula Differences of Existing XCH Preparations

Capsules, granules, pills, tablets, and other XCH preparations are all on the Chinese domestic market. Among those, XCH tablets, XCH effervescent tablets, XCH capsules, and XCH granules were included in the 2020 edition of the Chinese Pharmacopoeia [17]. The Pharmaceuticals and Medical Devices Agency in Japan [18] has published more than 10 kinds of XCH preparations, which are mainly granules or tablets. The Japanese Pharmacopoeia includes two different specifications of the Shosaikoto extract [19]. In Korea, Soshiho-Tang is widely used as a classic recommendation, which is mainly sold in granules [20].
The raw materials of the Japanese XCH preparations are Pinelliae Rhizoma, Ginseng Radix, Bupleuri Radix, Scutellariae Radix, Glycyrrhizae Radix, Zingiberis Rhizoma Recens, and Jujubae Fructus. However, the main XCH preparations on the Chinese market use Pinelliae Rhizoma Praeparatum Cum Zingibere Et Alumine (Jiangbanxia), Codonopsis Radix, Bupleuri Radix, Scutellariae Radix, Glycyrrhizae Radix, Zingiberis Rhizoma Recens, and Jujubae Fructus as raw materials. Table 1 shows four XCH preparations that are listed in the Chinese Pharmacopoeia. The JUN material Bupleuri Radix is the highest in mass ratio among the four dosage forms included in Chinese Pharmacopoeia, accounting for approximately 30%. The raw material mass ratio of XCH tablets and XCH capsules is exactly the same, and the mass ratio of Jiangbanxia is higher than those of XCH effervescent tablets and XCH granules. Regarding the materials of Japanese XCH preparations, the mass ratio of Pinelliae Rhizoma is lower than that of Bupleuri Radix but higher than that of any other herb. The mass ratio values of Glycyrrhizae Radix and Zingiberis Rhizoma Recens are both lower than 10%.
Table 1. Formula amount of raw materials, their mass ratio and preparation amount in different XCH preparations in pharmacopoeias.
Raw Materials XCH Tablets & XCH Capsules XCH Effervescent Tablets XCH Granules Shosaikoto Extract (Japanese)
— Amount (g) Mass Ratio (%) Amount (g) Mass Ratio (%) Amount (g) Mass Ratio (%) Amount (g) Mass Ratio (%) Amount (g) Mass Ratio (%)
Bupleuri Radix 445 29.6 1550 31.0 150 31.0 7 29.2 6 26.1
Jiangbanxia 222 14.8 575 11.5 56 11.5 - - - -
Pinelliae Rhizoma - - - - - - 5 20.8 5 21.7
Scutellariae Radix 167 11.1 575 11.5 56 11.5 3 12.5 3 13.0
Codonopsis Radix 167 11.1 575 11.5 56 11.5 - - - -
Ginseng Radix - - - - - - 3 12.5 3 13.0
Glycyrrhizae Radix 167 11.1 575 11.5 56 11.5 2 8.33 2 8.70
Zingiberis Rhizoma Recens 167 11.1 575 11.5 56 11.5 1 4.17 1 4.35
Jujubae Fructus 167 11.1 575 11.5 56 11.5 3 12.5 3 13.0
Preparation amount XCH tablets: 1000 tablets, 0.4 g each;
XCH capsules: 1000 capsules, 0.4 g each;		 XCH effervescent tablets: 1000 tablets, 2.5 g each XCH granules:
1000 g (combined with sucrose);
400 g (combined with mannitol);
250 g (combined with lactose)		 Not specified
Pinelliae Rhizoma can cause adverse reactions, such as mucosal irritation [21], hepatorenal toxicity [22], and pregnancy toxicity [23][24]. It has been reported that the needle crystals of calcium oxalate and its lectin protein contained in Pinelliae Rhizoma are the main irritant toxic substances [25][26]. In China, there is a long history to use Zingiberis Rhizoma Recens to alleviate the toxicity of Pinellia ternata. The processing standards for preparing Jiangbanxia have been established [27]. Therefore, the use of Jiangbanxia in XCH preparations in China is conducive to improving drug safety [28].
Table 1 compared the amount and mass ratio of raw materials in different XCH preparations which were included in the Chinese and Japanese Pharmacopoeia [17][19]. By having materials divided by the total weight, the mass ratios are calculated and listed.

2. Prospect on the Development Direction of Quality Control of XCH Preparations

2.1. Improvement in the Specificity of Quality Testing

According to Chinese Pharmacopoeia, Glycyrrhizae Radix, Bupleuri Radix and Codonopsis Radix are used as TLC reference materials, and baicalin is used as a TLC reference substance in qualitative identification. However, less attention has been given to Zingiberis Rhizoma Recens, Jujubae Fructus, and Jiangbanxia. The specific components of Jiangbanxia and Jujubae Fructus are not quantitatively analyzed in literature. Recently, guanosine, uridine, hypoxanthine and several other components were analyzed [29], which do not especially belong to Jiangbanxia, but it still suggests a way to improve the specificity of HPLC detection by detecting these compositions with strong polarity.
It is essential to distinguish the authenticity of Bupleuri Radix. There are 36 species, 17 varieties, and seven forms distributed all over China [30]. Among them, Bupleurum marginatum var. stenophyllum and even poisonous Bupleurum longiradiatum are common varieties that are all easy to mix up [31]. To confirm whether or not Bupleurum marginatum var. stenophyllum had been added, Liu et al. using the retention time and peak area of the specific ion detected in the mass spectrum as standards [32]. Liang et al. tried to establish near-infrared spectrum models to distinguish products of different factories, which provided a practical technology for low-cost and rapid detection [33]. Lai et al. used a polymerase chain reaction (PCR) method based on the site specificity of the Internal Transcribed Spacer (ITS) sequence to identify Bupleurum marginatum var. stenophyllum from Bupleurum chinense DC [34]. These new technologies provide ideas for improving the specificity of analytical methods. Bupleurum scorzonerifolium Willd and Bupleurum chinense DC are both included in the Chinese Pharmacopoeia, but National Institutes for Food and Drug Control can provide only the reference material of Bupleurum chinense DC. Hence, the lack of reference material of Bupleurum scorzonerifolium Willd is a problem for quality control of Bupleuri Radix.

2.2. Setting Reasonable Content Range of Index Components from Bupleuri Radix

Bupleuri Radix is the JUN of XCH formula. Thus far, qualitative identification using the reference material of Bupleuri Radix was adopted in Chinese Pharmacopoeia. However, considering drug safety and efficacy, the contents of saikosaponins should be controlled in specific ranges. Studies have indicated that saikosaponins are important active ingredients of Bupleuri Radix, which has antipyretic, anti-inflammatory and antitumor activities. Therefore, it is necessary to set up lower limits for their contents [35][36]. Moreover, some reference materials have reported that Bupleuri Radix has a certain degree of toxicity when taken in a large dose for a long period of time, and its toxic side effects are often caused by its saponins and volatile substances, which mainly affect the liver [37]. Therefore, from the perspective of drug safety, it is necessary to set up upper limits for saikosaponins. At present, the upper and lower limits of the saikosaponin B2 content are set up in the Japanese Pharmacopoeia, which is worth referencing. When setting up the lower limit, companies can consider collecting big data from clinical practice. Accordingly, the needs of drug quality control indicators can be taken into consideration, such as drug interactions and medications for special populations.

2.3. Strengthening the Standard of Limited Detected Items

In recent years, great progress in the control of heavy metals, pesticides, and biological toxins in Chinese medicines and extracts was achieved. The Chinese Pharmacopoeia has specially listed items General Principle for Inspection of Crude Drugs and Decoction Pieces and Guidelines for Establishment of Limit for Harmful Residue of Traditional Chinese Medicine, which have provided guidance for controlling heavy metals, pesticides and biological toxins for medicinal materials. The Chinese Pharmacopoeia stipulates that Jujubae Fructus needs to be tested for aflatoxin, Glycyrrhizae Radix needs to be tested for heavy metals, harmful elements and pesticide residues, and Codonopsis Radix needs to be tested for sulfur dioxide residues, all of which help to guarantee the safety of XCH preparations. However, the current guidelines for XCH preparations still require more relevant limiting items for heavy metals, pesticides and biological toxins, and other toxic ingredients. The Japanese Pharmacopoeia stipulates the limits of heavy metals and arsenic in XCH preparations. It takes the increase in heavy metals during the production process into account, which is more rigorous and improves the level of quality control.
Therefore, from the perspective of drug safety, XCH preparations require an upper limit for the amounts of certain active ingredients, heavy metals, pesticides, biotoxins, and other toxic components. Similar quality control problems exist for many other Chinese medicines. Therefore, the development direction of quality control presented in this work can also be referenced for that of other Chinese medicines.

References

  1. Liu, T.T.; Yao, K.W.; Duan, J.L.; Yu, Z.; Zhang, L.D. Efficacy of Xiaochaihu Decoction on Treating Coronary Heart Disease. Lishizhen Med. Mater. Med. Res. 2019, 30, 2216–2218.
  2. Zhang, W.Z.; Nie, H.; Wang, Z.T.; Mao, D.X. Discussion of ginseng used in Xiaochaihu Decoction. Lishizhen Med. Mater. Med. Res. 2013, 24, 2480–2481.
  3. Zhang, Y.; Zhou, X.L.; Shao, Q.; Fang, Z.E.; Wang, S.S. Anti-inflammatory effect of Xiaochaihutang in rats with collagen-induced arthritis and the mechanism. Immunol. J. 2015, 31, 781–785.
  4. Zhai, Y.X.; Zhao, Y.; Xiang, R.W.; Zhai, F.; Zeng, Y.; Liang, J.K. Study on anti-heatoma mechanism of Xiaochaihu decoction based on weighted network pharmacology. Chin. J. Med. Chem. 2020, 30, 658–668.
  5. Lu, X.W.; Zhu, L.H.; Huang, H.; He, K. Clinical Observations on Modified Xiao Chaihutang in Treatment of Subacute Thyroiditis. Chin. J. Exp. Tradit. Med. Formulae 2018, 22, 153–158.
  6. Zhang, W.Z.; Tian, H.Z.; Zhang, L.J.; Yang, S.J. Clinical Study and Analysis of Modified Xiaochaihu Decoction in Treating Cough Caused by Variant Asthma. World J. Integr. Tradit. Western Med. 2020, 15, 790–793.
  7. Liu, L.; Wang, C.X.; Cui, S.Y.; Zhang, H.X.; Wu, X.X.; Zhang, W. Observation of curative effect of lamivudine combined with compound glycyrrhizin and Xiaochaihu Decoction in the treatment of chronic hepatitis B. Modern J. Integr. Tradit. Chin. Western Med. 2020, 29, 4042–4045.
  8. Luo, X.M. Clinical observation on treating chronic renal failure with the Xiaochaihu decoction. Clin. J. Chin. Med. 2012, 4, 99.
  9. Wang, D.X.; Liu, X.Z.; Lv, C.Y.; Fan, H.; Sun, Y.F.; Yang, S.L. Changes of Platelet- Associated Parameters in Patients with Refractory Immune Thrombocytopenia Treated with Xiaochaihu Decoction and Erzhi Pill. J. Hebei North Univ. Nat. Sci. Ed. 2020, 36, 5–9.
  10. Jiang, M. Effect observation of Minor Decoction of Bupleurum treating acute viral myocarditis. World Latest Med. Inf. 2015, 15, 1–14.
  11. Ma, R.; Liu, H.; Zheng, R.W.; Xu, Z.T.; Jiang, Z.Q.; Zhang, J.H.; Jiang, Y.F.Y.; Bi, C. Pharmacological analysis and confirmation of antipyretic mechanism of Xiaochaihu Granules. J. Pharm. Res. 2021, 8, 497–503.
  12. Li, X.; Li, Y.Y.; Wen, C.X.; Liang, Y.Y.; Zhou, Z.L. Study on the mechanism of Xiaochaihu Decoction in treatment of hepatocellular carcinoma based on network pharmacology and bioinformatics. Anti-Tumor Pharm. 2021, 4, 456–462.
  13. Ma, R.; Liu, H.; Jiang, Y.F.Y.; Zheng, R.; Jiang, Z.Q.; Bi, C.; Zhang, J.H.; He, Y.X.; Du, H.Y. A New Use of Xiaochaihu Granules Combined with Antibiotics. Guangdong Province Patent CN111529671A, 14 August 2020.
  14. Liu, H.; Huang, W.; Cheng, X.Y.; Bi, C.; Zheng, R.W.; Jiang, Z.Q.; Zhang, J.H.; He, Y.X.; Du, H.Y. New Application of Xiaochaihu Granules in the Control of Syncytial Virus and Adenovirus. Patent CN111467466A, 31 July 2020.
  15. Zheng, R.W.; Liu, H.; Situ, W.H.; Jiang, Z.Q.; Bi, C.; Zhang, J.; He, Y.X.; Du, H.Y. New Application of Xiaochaihu Granules in Inhibiting Influenza a Virus. Patent CN111358929A, 3 July 2020.
  16. China National Knowledge Infrastructure. Available online: https://kns.cnki.net/kns8/defaultresult/index (accessed on 9 October 2021).
  17. Chinese Pharmacopoeia Commission. The Chinese Pharmacopoeia; China Medical Science Press: Beijing, China, 2020; pp. 602–606.
  18. Pharmaceuticals and Medical Devices Agency. Available online: https://www.pmda.go.jp/PmdaSearch/iyakuSearch/ (accessed on 22 September 2021).
  19. Japanese Pharmacopoeia Committee. The Japanese Pharmacopoeia, 17th ed.; The Ministry of Health, Labour and Welfare: Tokyo, Japan, 2016; pp. 1988–1990.
  20. Kim, H.M.; Kim, Y.Y.; Jang, H.Y.; Moon, S.J.; An, N.H. Action of Sosiho-Tang on systemic and local anaphylaxis by anal administration. Immunopharm. Immunot. 1999, 21, 635–643.
  21. Zhong, L.Y.; Wu, H. Current researching situation of mucosal irritant components in Acacae family plants. China J. Tradit. Chin. Med. Pharm. 2006, 18, 1561–1563.
  22. Zhang, L.M.; Bao, Z.Y.; Huang, Y.Y.; Huang, W.; Zhang, Y.N.; Sun, R. Experimental Study on the “Dosage-Time-Toxicity” Relationship of Acute Hepatotoxicity induced by Water Extraction from Rhizoma Pinelliae in Mice. Chin. J. Pharmacovigil. 2011, 8, 11–15.
  23. Jin, X.Q.; Huang, C.Q.; Zhang, G. Toxic Components and Processing Mechanism of Rhizoma Pinelliae. Lishizhen Med. Mater. Med. Res. 2019, 30, 1717–1720.
  24. Zhang, K.; Shan, J.J.; Xu, J.Y.; Wang, M.M. Research progress and prospects of pregnancy toxicity of pinellia. China J. Tradit. Chin. Med. Pharm. 2016, 31, 938–941.
  25. Zhu, F.G.; Yu, H.L.; Wu, H.; Shi, R.J.; Tao, W.T.; Qiu, Y.Y. Correlation of Pinellia ternata agglutinin and Pinellia ternata raphides’ toxicity. China J. Chin. Mater. Med. 2012, 37, 1007–1011.
  26. Zhong, L.Y.; Wu, H.; Zhang, K.W.; Wang, Q.R. Study on irritation of calcium oxalate crystal in raw Pinellia ternate. China J. Chin. Mater. Med. 2006, 20, 1706–1710.
  27. Su, T.; Zhang, W.W.; Zhang, Y.M.; Cheng, C.Y.B.; Fu, X.Q.; Li, T.; Guo, H.; Li, Y.X.; Zhu, P.L.; Cao, H.; et al. Standardization of the manufacturing procedure for Pinelliae Rhizoma Praeparatum cum Zingibere et Alumine. J. Ethnopharmacol. 2016, 193, 663–669.
  28. Shi, R.J.; Wu, H.; Yu, H.L.; Chen, L. The advance of the research that zingiber officinale rosc detoxify the tuber of pinellia. Chin. J. Inf. Tradit. Chin. Med. 2010, 17, 108–110.
  29. Chen, W.; Zhang, C.; Sun, L.; Xue, M. Combination of fingerprint and chemometrics for identification of four processed products of Pinelliae Rhizoma based on nucleosides and nucleobases. Chin. J. Pharm. Anal. 2021, 41, 919–928.
  30. Chinese Academy of Sciences. Flora of China. Available online: http://www.iplant.cn/info/Bupleurum?t=z (accessed on 28 July 2021).
  31. Zhao, J.F.; Guo, Y.Z.; Meng, X.S. The toxic principles of Bupleurum longiradiatum. Acta Pharm. Sin. 1987, 7, 507–511.
  32. Liu, X.X.; Luo, Z.Y.; Ji, Z.Z.; Li, H.; Zhang, W.Q.; Chen, F. A Detection Method of Adulteration of B. Marginatum var.Stenophyllum in Xiaochaihu Granules Preparation and Its Chinese Herbal Medicine Raw Materials. Patent CN110779993A, 11 February 2020.
  33. Liang, H.L.; Tan, C.C.; Jiang, X.J.; Xiao, X.Y.; Xu, W.B. Study on Rapid Identification on Xiaochaihu Granules from Different Manufacturers by Near Infrared Spectroscopy. Guiding J. Tradit. Chin. Med. Pharm. 2021, 27, 62–64.
  34. Lai, J.; Shi, Z.F.; Song, P.S.; Wang, Z.X.; Ni, L.; Teng, B.X. Identification of Bupleurum marginatum var.stenophyllum Adulterated Bupleurum chinese by PCR Amplification of Based on ITS Sequences. Res. Pract. Chin. Med. 2021, 35, 18–21.
  35. Xie, D.H.; Cai, B.C.; An, Y.Q.; Li, X.; Jia, X.B. The research progerss in saikosaponin and its pharmacology action. J. Nanjing Univ. Tradit. Chin. Med. 2007, 1, 63–65.
  36. Lv, X.H.; Sun, Z.X.; Su, R.Q.; Fan, J.W.; Zhao, Z.Q. The pharmacology research progress in bupleurum and its active constituents. Chin. J. Inf. Tradit. Chin. Med. 2012, 29, 105–107.
  37. Liu, Y.M.; Liu, X.M.; Pan, R.L. The research progress in toxic effect of bupleurum. Chin. Tradit. Pat. Med. 2012, 34, 1148–1151.
More
© Text is available under the terms and conditions of the Creative Commons Attribution (CC BY) license; additional terms may apply. By using this site, you agree to the Terms and Conditions and Privacy Policy.
Upload a video for this entry
Information
Subjects: Integrative & Complementary Medicine
Contributor MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register :
Guangzheng Xu
View Times: 415
Revisions: 2 times (View History)
Update Date: 21 Dec 2021
Table of Contents
    1000/1000
    Hot Most Recent
    Feedback