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Chinese Medicine

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Fecal medicines used in traditional medical system of China: a systematic review of their names, original species, traditional uses, and modern investigations

  • Huan Du
  • Ting-ting Kuang
  • Shuang Qiu
  • Tong Xu
  • Chen-Lei Gang Huan
  • Gang FanEmail author
  • Yi Zhang
Open Access
Review
  • 188 Downloads

Abstract

In China, the medical use of fecal matter (fresh fecal suspension or dry feces) can be dated back to the fourth century, approximately 1700 years ago. In long-term clinical practice, Chinese doctors have accumulated unique and invaluable medical experience in the use of fecal materials. In view of their good curative effect and medicinal potential, fecal medicines should be paid much attention. This study aimed to provide the first comprehensive data compilation of fecal medicines used in various Chinese traditional medical systems by bibliographic investigation of 31 medicine monographs and standards. A total of 54 fecal medicines were found to be used in 14 traditional Chinese medical systems. Their names, original species, medicinal forms, and traditional uses were described in detail. These fecal medicines were commonly used to treat gastrointestinal, nervous system, skin, and gynecological diseases. Commonly used fecal medicines include Wu-Ling-Zhi, Jiu-Fen and Hei-Bing-Pian. The information summarized in this study can provide a good reference for the development and utilization of fecal medicines. Further studies are necessary to prove their medicinal value, identify their active ingredients, and elucidate their mechanisms of action so that more people can accept these special medicines.

Keywords

Fecal medicines Traditional Chinese medicine Gut microbiota Fecal microbiota transplantation Gastrointestinal diseases 

Abbreviations

TCM

traditional Chinese medicine

TTM

traditional Tibetan medicine

EM

ethnic medicine

Background

Traditional medicines have been used for prevention and treatment of diseases for thousands of years in China. In recent decades, they have attracted worldwide attention due to their reliable therapeutic efficacy and low side effects. During the long-term struggle against diseases, ancient Chinese doctors found that some unexpected materials, such as human or animal feces, could also effectively treat diseases. In China, the medical use of fecal matter (fresh fecal suspension or dry feces) has a long history. During the Eastern Jin dynasty (ad 300–400 years), “Zhou Hou Bei Ji Fang”, a well-known monograph of traditional Chinese medicine (TCM) written by Hong Ge, recorded a case of treating patients with food poisoning or severe diarrhea by ingesting human fecal suspension (known as yellow soup or Huang-Long decoction) [1]. During the Tang dynasty, Yutuo Ningma Yundan Gongbu compiled a world-famous book of Tibetan medicine called “The Four Medical Tantras”, which recorded that digestive diseases can be treated with the processed product of the feces of Sus scrofa (Hei-Bing-Pian in Chinese) [2]. Later, the “Compendium of Materia Medica” (a masterpiece of herbalism written by Shizhen Li during the Ming dynasty) described a series of prescriptions for treating diarrhea, rheumatism, jaundice, fever, and pain using fresh fecal suspension or dry feces [3]. In addition, “Jing Zhu Materia Medica” written by Danzeng Pengcuo Dimaer in the nineteenth century recorded that Hei-Bing-Pian and the dry feces of Gypaetus barbatus or Aegypius monachus (Jiu-Fen in Chinese) are commonly used to treat dyspepsia and gastric ulcer [4]. These records indicate that fecal medicines are widely used and occupy an important position in Chinese traditional medical systems.

In long-term clinical practice, Chinese doctors have accumulated unique experience in the use of fecal medicines. For example, the dry feces of Trogopterus xanthipes (Wu-Ling-Zhi in Chinese) is often used to treat blood stasis, swelling and aching due to traumatic injury [5]. Jiu-Fen is good at treating gastrointestinal diseases, such as dyspepsia, weak gastrointestinal function and gastric ulcer. Hei-Bing-Pian can treat diseases, such as indigestion, diarrhea and distending pain in the stomach [6]. These traditional medication experiences are undoubtedly valuable assets and can provide a reference for modern drug development. However, documents on the traditional use of fecal medicines are scattered and lack systematic collation.

In this review, we comprehensively collect and summarize the names, origins, and treated diseases of fecal medicines that have been used in some Chinese traditional medical systems, including TCM, Tibetan ethnic medicine (EM), Oroqen EM, Kazak EM, Uygur EM, Mongolian EM, Nu EM, Yao EM, Wa EM, Tujia EM, Korean EM, Jino EM, Hani EM, and Dai EM. In addition, we review the most frequently used fecal medicines in terms of their origins, traditional uses, chemical constituents, and pharmacological activities. Such information can provide a good reference for their development and utilization. These fecal medicines may be a valuable gift from Chinese traditional medicine to the world and has potential as drug candidates for the treatment of some chronic diseases, such as gastrointestinal diseases.

Methods

We have manually searched 31 related medicine monographs and drug standards, such as “Zhou Hou Bei Ji Fang”, “Compendium of Materia Medica”, “Jing Zhu Materia Medica”, “Dictionary of Chinese Ethnic Medicine”, “Drug Standards of Tibetan Medicine”, “Lan Liu Li”, “Pharmacopoeia of the People’s Republic of China”, and “Chinese Tibetan Materia Medica”, to obtain the information about the names, origins, traditional uses, and treated diseases of fecal medicines. In addition, we have searched the online Chinese literature databases (i.e., Wan fang and CNKI) and international English databases (i.e., PubMed, ISI Web of Science and Google Scholar), using their vernacular or Latin names as keywords, to obtain their chemical constituents and biological effects.

Results

This review recorded 54 fecal medicines that have been used in 14 Chinese traditional medical systems. Their names, original species, medicinal forms, and treated diseases are presented in Tables 1 and 2. These 54 medicines mainly originate from the feces of 56 animals. Among medicinal forms used, dry feces is the most frequently used (66.67%), followed by processed feces (29.63%) and fresh fecal juice (3.70%). In addition, we found that these 54 fecal medicines are mainly used to treat gastrointestinal (37.04%), nervous system (22.22%), skin (22.22%), ophthalmic (18.52%), and gynecological diseases (16.67%).
Table 1

Fecal medicines used in the traditional Chinese medicine (TCM) system

No.

Animal species

Medicinal form

Chinese name

Traditional uses (treated diseases)

Refs.

1

Trogopterus xanthipes Milne-Edwards

Dry feces

Wu-Ling-Zhi

Stabbing pain in chest and abdomen, dysmenorrhea, amenorrhea, swelling and aching due to traumatic injury, and snake bites

[5, 8, 52]

2

Bombyx mori L.

Dry feces

Can-Sha

Rheumatism, arthralgia, skin numbness, cold pain in waist and legs, rubella itching, and headache

[3, 52]

3

Vespertilio superans Thomas

Dry feces

Ye-Ming-Sha

Night blindness, swelling and pain in the eyes, infantile malnutrition, scrofula, and malaria

[5, 53]

Rhinolophus ferrumequinum Schreber

Plecotus auritus L.

Hipposideros armiger Hodgson

4

Lepus mandschuricus Radde

Dry feces

Wang-Yue-Sha

Blurred vision, hemorrhoids and fistula, and infantile malnutrition

[52, 54, 55]

Lepus sinensis Gray

Lepus oiostolus Hodgson

5

Gallus gallus domesticus Brisson

Dry feces

Ji-Shi-Bai

Jaundice, gonorrhea, wandering arthritis, tetanus, spasm of muscles and tendons, and diabetes

[3, 56]

6

Rattus flavipectus Milne-Edwards

Dry feces

Liang-Tou-Jian

Fever due to typhoid, abdominal pain, stranguria with turbid urine, amenorrhea, infantile malnutrition, mammary abscess, and furuncle

[56, 57, 58]

Rattus norvegicus Berkenhout

7

Columba livia domestica L.

Dry feces

Zuo-Pan-Long

Abdominal mass, scrofula and tetanus

[3, 57]

8

Physeter macrocephalus L.

Dry feces

Long-Xian-Xiang

Coma due to stuffiness, abdominal pain, cough and dyspnea, and gonorrhea

[52, 56]

9

Passer montanus L.

Dry feces

Bai-Ding-Xiang

Abdominal mass, carbuncle and furuncle, blurred vision, pterygium, and dental caries

[55, 56, 58]

10

Homo sapiens

Fresh fecal juice

Yellow soup or Huang-Long decoction

Food poisoning, severe diarrhea, heat toxin, and unconsciousness due to high fever

[1, 3]

11

Hirundo daurica L.

Dry feces

Yan-Zi-Fen

Edema, malaria, insect poison, ulcer and sore

[3, 56]

12

Pavo muticus L.

Dry feces

Kong-Que-Fen

Excessive leucorrhea in women, dysuria and furuncle

[3, 56]

13

Bos taurus domesticus Gmelin

Fresh fecal juice or dry feces

Niu-Fen

Fresh fecal juice can cure jaundice caused by diabetes, beriberi, cholera, and dysuria; dry feces can treat malignant sore, cervical lymph node and tuberculosis fistula

[3, 56]

Bubalus bubalis L.

14

Ochotona thibetana Milne-Edwards

Dry feces

Cao-Ling-Zhi

Irregular menstruation, stagnant abdominal pain, stomach pain, traumatic injury, and blood stasis

[56, 57]

Ochotona erythrotis Buchner

Table 2

Fecal medicines used in other traditional ethnic medicine (EM) systems in China

No.

Animal species

Medicinal form

Traditional medical systems

Traditional uses (treated diseases)

Refs.

1

Gypaetus barbatus L.

Dry feces

Tibetan EM and mongolian EM

Dyspepsia, abdominal distension, intestinal tumor, gastric ulcer, weak gastrointestinal function, sores and carbuncles

[2, 4, 6]

Aegypius monachus L.

2

Sus scrofa L.

Processed feces

Tibetan EM and mongolian EM

Dyspepsia, biliary diseases, plague and distending pain of stomach

[6, 36, 59]

3

Sus scrofa domestica Brisson

Processed feces

Tibetan EM

Dyspepsia, plague and biliary tumor

[4, 36, 60]

4

Petaurista xanthotis Milne-Edwards

Dry feces

Tibetan EM

Stomach pain, amenorrhea and dysmenorrhea

[59, 60]

5

Pteromys volans L.

Dry feces

Oroqen EM

Dysentery and diarrhea

[60]

Kazak EM

Metrorrhagia, amenorrhea, and snake bites (external use)

[60]

Uygur EM

Eczema, itching, amenorrhea, dysmenorrhea, stomach pain, and traumatic injury

[61]

6

Riparia riparia L.

Processed feces

Tibetan EM

Bloody dysentery, chronic diarrhea, women amenorrhea, and hematuria

[59, 60]

7

Felis ocreata domestica Brisson

Processed feces

Tibetan EM

Manic psychosis or madness

[36, 60]

8

Upupa epops L.

Processed feces

Tibetan EM

Psychopathy

[4, 59]

9

Vulpes vulpes L.

Dry feces

Tibetan EM

Psychopathy and epilepsy

[4, 60]

10

Trogopterus xanthipes Milne-Edwards

Dry feces

Mongolian EM

Diarrhea, gout and itching

[62]

Nu EM

Cold, whooping cough and fever

[60]

Tibetan EM

Stomach pain, dysmenorrhea and amenorrhea

[59, 60]

Tujia EM

Blood stasis, furuncles, traumatic injury, dysmenorrhea, and snake bites (external use)

[60]

Korean EM

Stabbing pain in chest and abdomen, dysmenorrhea, amenorrhea, swelling and aching due to traumatic injury

[60]

Dai EM

Amenorrhea, dysmenorrhea, pain due to blood stasis, and snake bites (external use)

[60]

Yao EM

Dysmenorrhea, amenorrhea, and epilepsy

[63]

11

Pipistrellus abramus Temminck

Dry feces

Wa EM

Asthma, burn, night blindness, and infantile malnutrition

[60]

Tibetan EM

Epilepsy

[4, 60]

Tujia EM

Night blindness, cataract, infantile malnutrition, and corneal nebula

[64]

12

Vespertilio superans Thomas

Dry feces

Korean EM

Night blindness, intermittent fever, cataract, and underarm odor

[60]

Yao EM

Night blindness, corneal nebula, infantile malnutrition, and scrofula

[63]

13

Plecotus kozlovi Bobrinski

Processed feces

Tibetan EM

Eye diseases, scrofula and infantile malnutrition

[60]

14

Myotis mystacinus Kuhl

Processed feces

Tibetan EM

Psychosis and epilepsy

[60]

15

Lepus capensis L.

Dry feces

Tibetan EM

Blurred vision, hemorrhoids and fistula, and infantile malnutrition

[4, 59]

16

Equus caballus orientalis Noack

Processed feces

Tibetan EM

Various parasitic diseases and vomiting

[65, 66]

17

Gallus gallus domesticus Brisson

Dry feces

Korean EM

Jaundice, gonorrhea, tetanus, and diabetes

[60]

Tibetan EM

Eye diseases

[4, 60]

Dai EM

Shoulder arthritis, tetanus and corneal scar

[60]

18

Rattus rattus L.

Dry feces

Tibetan EM

Epilepsy

[59, 60]

19

Physeter macrocephalus L.

Dry feces

Uygur EM

Neurasthenia, memory loss and psychological impotence

[60]

20

Passer montanus L.

Dry feces

Jino EM

Manic psychosis or madness

[60]

Hani EM

Hernia

Tibetan EM

Sores and furuncles (external use)

[59, 60]

21

Columba rupestris Pallas

Dry feces

Tibetan EM

Swelling and suppuration

[2, 60]

22

Pavo muticus L.

Processed feces

Tibetan EM

Inflammation

[4, 36, 59]

23

Bos taurus domesticus Gmelin

Processed feces

Tibetan EM

Food poisoning, limbs pain, and spasm

[4, 36, 59]

24

Canis lupus L.

Processed feces

Tibetan EM and mongolian EM

Psychopathy and swelling

[4, 59]

25

Tetraogallus tibetanus Gould

Dry feces

Tibetan EM

Various swelling

[2, 36]

26

Bubo bubo hemachalana Hume

Processed feces

Tibetan EM

Psychopathy and epilepsy

[4, 59, 67]

27

Pica pica L.

Dry feces

Tibetan EM

Skin diseases, such as sores and furuncles

[59, 60]

28

Streptopelia orientalis Latham

Dry feces

Uygur EM

Purulent secretion of the ear; Pain caused by ear diseases

[61]

29

Corvus corax L.

Processed feces

Tibetan EM

Bromhidrosis, epilepsy, cough, and psychopathy

[59, 60]

30

Canis lupus familiaris L.

Processed feces

Tibetan EM

Psychopathy and swelling; Syphilis, psoriasis and anthracnose (external use)

[4, 59, 60]

31

Elephas maximus L.

Dry feces

Dai EM

Ophthalmitis

[60]

32

Equus asinus L.

Processed feces

Tibetan EM

Sores and furuncles (external use) and rabies

[4, 59]

33

Phalacrocorax carbo L.

Dry feces

Korean EM

Pigmented naevus (external use)

[60]

34

Buteo hemilasius Temminck et Schlegel

Dry feces

Tibetan EM

Sores and furuncles (external use)

[4, 59]

35

Macaca mulatta Zimmermann

Dry feces

Tibetan EM

Inflammation, swelling and dysentery

[59, 60]

36

Ovis aries L.

Dry feces

Tibetan EM

“Huang-Shui” disease in arms and legs (external fumigation)

[59, 60]

37

Capra hircus L.

Dry feces

Tibetan EM

Heat toxin syndrome, nervous system diseases and leprosy

[4, 60]

Korean EM

Child dysentery, borborygmus and convulsive epilepsy

[60]

38

Tetrao urogalloides Middendorf

Dry feces

Tibetan EM

Psychopathy and swelling

[4]

39

Lutra lutra L.

Processed feces

Tibetan EM

Uterine diseases

[4, 60]

40

Moschus sifanicus Przewalski

Dry feces

Tibetan EM

Limb numbness, paralysis and blood stasis

[4, 36, 59]

Fecal medicines used in the TCM system

Traditional Chinese medicine is the most representative traditional medical system in China. It has a long history of more than 2500 years. In recent decades, TCM has attracted global attention due to its reliable therapeutic efficacy. Generally, TCM uses herbs, animals or minerals to treat diseases. In long-term clinical practices, animal feces have been found to be effective in treating some specific diseases under the guidance of TCM theory. As early as the Eastern Jin dynasty, human fecal juice (i.e., yellow soup) has been used by TCM practitioners to treat severe diarrhea [1]. At present, some fecal medicines are still used in the clinical practice of TCM. In the 2015 edition of Chinese Pharmacopoeia [7], 18 preparations have been found to contain fecal medicines (Table 5). For example, “Shi-Xiang-Zhi-Tong Powder” and “Tong-Jing Pills” contain Wu-Ling-Zhi, and “Huang-Lian-Yang-Gan Pills” contains Ye-Ming-Sha (dry feces of some kinds of bats).

In the present study, a bibliographic investigation of TCM monographs and drug standards revealed 14 kinds of fecal medicines that are commonly used in the TCM system. They mainly come from the feces of 22 animals and are widely used to treat dysmenorrhea, amenorrhea, abdominal mass, diarrhea, and blurred vision. Additional information on these 14 medicines is provided in Table 1. Wu-Ling-Zhi is the most representative fecal medicine in the TCM system (Fig. 1). Therefore, its traditional uses, chemical constituents and pharmacological activities are described in detail in the subsequent sections.
Fig. 1

The commonly used fecal medicines in traditional medical system of China (a Ye-Ming-Sha; b Wu-Ling-Zhi; c Can-Sha; d Jiu-Fen; e Hei-Bing-Pian)

The dry feces of Trogopterus xanthipes (Wu-Ling-Zhi in Chinese)

Wu-Ling-Zhi (Fig. 1b), also named as Goreishi or Trogopterorum faeces, is one of the commonly used fecal medicines. It derives from the dry feces of Trogopterus xanthipes. Wu-Ling-Zhi was first recorded in the classic Chinese medicinal book “Kai Bao Ben Cao” compiled in the Song Dynasty [8]. Its traditional uses were described in several TCM monographs and drug standards. For example, “Ben Cao Jing Shu” recorded that Wu-Ling-Zhi had a good therapeutic effect on stabbing pain caused by blood stasis [9]. In addition, the Chinese Pharmacopoeia 1990 edition recorded that Wu-Ling-Zhi had good effects of promoting blood circulation, removing blood stasis and relieving pain, and was usually used to treat the stabbing pain in the chest and hypochondrium, dysmenorrhea, amenorrhea, swelling and aching due to traumatic injury, postpartum blood stasis, and snake bites.

So far, some chemical constituents categorized as terpenoids, flavonoids, lignans, sterols, and esters have been isolated from Wu-ling-zhi. The chemical structures of representative compounds are shown in Fig. 2. Numata et al. [10] found that the feces of T. xanthipes contain several cytotoxic triterpenes, namely, pomolic acid, 3-O-cis-p-coumaroyltormentic acid, 2α-hydroxyursolic acid, and jacoumaric acid. Subsequently, they isolated three new ursane-type triterpenes (i.e., goreishic acids I, II and III) from the feces of T. xanthipes in 1990 [11]. In addition, 19 diterpenoids including three new isopimarane diterpenoids (trogopteroids A–C) and four new aromatic diterpenoids (trogopteroids D–G) were isolated from the feces of T. xanthipes [12]. Yang et al. [13] also isolated two new diterpenoids (wulingzhic acid A and wulingzhic acid B) from the feces of T. xanthipes. Additionally, the isolation and structural elucidation of flavonoids in Wu-Ling-Zhi were done by Yang et al. [14]. Seven flavonoids such as kaempferol 3-O-α-l-(4″E-p-coumaroyl)-rhamnoside, hinokiflavone, afzelin, and quercitrin were found. In 2012, four new neolignans were obtained from the ethyl acetate fraction of methanol extract of Wu-Ling-Zhi [15]. Subsequently, they also isolated neolignans that had been reported before from its methanolic extract and named trogopterins A–C [16]. Moreover, Yang et al. [17] isolated four new fatty acid esters from the feces of T. xanthipes. Currently, it was reported that dihydrositosterol, epifriedelanol, 5-methoxy-7-hydroxycoumarin, β-sitosterol, ursolic acid, protocatechuic acid, and daucosterol were also isolated from Wu-Ling-Zhi [18, 19]. Moreover, some volatile compounds identified by capillary gas chromatography combined mass spectrometry were also found in Wu-ling-zhi, such as dodecanoic acid, alpha-cedrol, tetradecanoic acid, and benzaldehyde [20].
Fig. 2

Chemical structures of representative compounds isolated from Wu-Ling-Zhi and Hei-Bing-Pian

At present, there are some studies involving the quality control of Wu-Ling-Zhi. Yerigui et al. [21] quantified five bile acids (i.e., cholic acid, deoxycholic acid, lithocholic acid, ursodeoxycholic acid, and taurocholic acid) in Wu-Ling-Zhi by using ultra high-performance liquid chromatography-mass spectrometry. Jiao et al. [22] established a thin layer chromatography (TLC) method for qualitative identification of Wu-Ling-Zhi, and developed a high performance liquid chromatography (HPLC) method to simultaneously quantify three active ingredients (protocatechuic acid, hinokiflavone and amentoflavone) in Wu-Ling-Zhi. Recently, Chen et al. also established the quality standard of Wu-Ling-Zhi. They qualitatively and quantitatively analyzed quercetin, kaempferol and amentoflavone in Wu-Ling-Zhi by TLC and HPLC, respectively [23]. These results can provide important reference for the quality control of Wu-Ling-Zhi.

Moreover, it is worth pointing out that extracts or chemical constituents obtained from the Wu-Ling-Zhi have been proved to possess a wide spectrum of pharmacological activities, such as anti-inflammatory, anti-cerebral ischemia, anti-gastric ulcer, and antithrombin effects. The basic pharmacological data of Wu-Ling-Zhi extracts and some isolated compounds are shown in Tables 3 and 4. Kim et al. [24] reported that Wu-Ling-Zhi extract could reduce lipopolysaccharide-induced NO and cytokines production. Wang et al. [25] found that the ethyl acetate extract of Wu-Ling-Zhi showed obvious inhibitory effects on xylene-induced ear swelling in mice and carrageenan-induced paw swelling in rats (400 mg/kg, ip), and it could also significantly inhibit the proliferation of granulation tissue in mice (800 mg/kg, ip). These findings indicated that Wu-Ling-Zhi has obvious anti-inflammatory effect. Furthermore, the ethyl acetate extract of Wu-Ling-Zhi was also found to be able to protect gastric mucosa and prevent experimental gastric ulcer by inhibiting gastric acid secretion [26]. It was reported that the aqueous extract of Wu-Ling-Zhi could significantly prolong the survival time of mice with incomplete cerebral ischemia, reduce the brain water content, brain index and malondialdehyde (MDA) level, and increase superoxide dismutase (SOD) activity in rats, indicating that Wu-Ling-Zhi has good protective effect against cerebral ischemia [27]. Moreover, the aqueous extract of Wu-Ling-Zhi could down-regulate the expression of intercellular adhesion molecule-1 in experimental atherosclerotic rats and reduce the degree of vascular endothelial lesions, which may account for the anti-arteriosclerosis inflammatory effects of Wu-Ling-Zhi [28]. Currently, several compounds isolated from Wu-Ling-Zhi, such as 3-O-α-l-(2″E,4″E-di-p-coumaroyl)-rhamnoside, bis(7-hydroxyheptyl) decanedioate and bis(7-hydroxyheptyl) octanedioate, were found to have significant antithrombin activity [14, 17]. Besides, a recent study showed that Wu-Ling-Zhi could trigger caspase dependent apoptosis in breast cancer cells (MCF-7 cells) [29].
Table 3

Pharmacological activities and mechanisms of some compounds isolated from Wu-Ling-Zhi and Hei-Bing-Pian

Name

Classification

Compound

Pharmacological activity

Effect and mechanism

Refs.

Wu-Ling-Zhi

Terpenoids

Tormentic acid

Antiangiogenic activity

Controlling abnormal proliferation and cell death resistance of vascular smooth muscle cell without affecting the normal vasculature

[68]

Euscaphic acid

Anti-inflammatory activity

Inhibition of LPS-induced inflammatory responses by interference with the clustering of TRAF6 with IRAK1 and TAK1

[69]

Jacoumaric acid

Cytotoxic activity

Significant cytotoxicity effect against P-388 lymphocytic leukemia cell

[10]

3-O-cis-p-coumaroy ltormentic acid

2α-hydroxy ursolic acid

Anticancer activity

Inhibition of cell proliferation and induction of apoptosis by regulating the p38/MAPK signal transduction pathway

[70]

Pomolic acid

Anti-inflammatory and apoptotic activities

Inhibiting inflammatory response by regulating human neutrophil function

[71]

Ursolic acid

Anticancer and anti-inflammatory activities

Inhibition of tumor growth and induction of apoptosis by modulating the MAPK/ERK and PI3 K/AKT/mTOR pathways; Inhibiting inflammation by suppression of NF-κB, AP-1 and NF-AT activity

[72]

Maslinic acid

Anticancer activity

It can significantly suppress pancreatic tumor growth, induce tumor apoptosis and inhibit NF-κB-regulated anti-apoptotic gene expression

[73]

Wulingzhic acid

Anticoagulative activity

Prolongation of thrombin time and inhibiting platelet aggregation

[13, 19]

Wulingzhic acid A

Wulingzhic acid B

Trogopteroids A–G

Cytotoxic activity

Cytotoxicity effect against seven human tumor cells, such as HepG2, HL-60 and U937

[12]

8β-hydroxy-3-oxopimara-15-ene

Akhdardiol

Isopimara-7(8),15-dien-3β-ol

Isopimara-8,15-dien-3β-ol

Sempervirol

Macrophynin E

Ferruginol

Gastroprotective activity

Increasing PGs content, protecting cells from lipid peroxidation and improving gastric ulcer healing

[74]

Epifriedelanol

Antioxidant and anti-inflammatory activities

Attenuating the secondary injury in TBI rats by reducing serum cytokine levels and oxidative stress

[75]

Flavonoids

Hinokiflavone

Anti-inflammatory activity

Inhibiting the LPS-induced expression of iNOS and COX-2 and the activation of NF-κB and ERK-1/2

[76]

Amentoflavone

Anti-diabetic activity

Regulating glucose and lipid metabolism via anti-oxidant effects and activating the PI3K/Akt pathway

[77]

Kaempferol-3-O-α-l-(2″E,4″E-di-p-coumaroyl)-rhamnoside

Anticoagulative activity

Significant prolongation of thrombin time

[14]

Kaempferol-3-O-α-l-(3″E,4″E-di-p-coumaroyl)-rhamnoside

Kaempferol-3-O-α-l-(4″E-p-coumaroyl)-rhamnoside

Afzelin

Antioxidant and anti-inflammatory activities

Inhibiting particulate matter-induced proinflammatory cytokine mRNA expression and protein secretion; Inhibiting intracellular ROS generation, and p38 mitogen-activated protein kinase and transcription factor activator protein-1 component c-Fos and c-Jun activation

[78]

Quercitrin

Gastroprotective and antioxidant activities

Inhibition of oxidative stress, regulation of mitochondrial dysfunction, and initiation of antioxidant defense

[79]

Lignans

Trogopterins A, B, and C

Cytotoxic activity

Cytotoxicity effect against different types of cancer cells, such as HL-60, HeLa, and MCF-7

[16]

Steroids

Daucosterol

Anti-colitis activity

Inhibiting dextran sulfate sodium (DSS)-induced colitis in mice by relieving inflammation and restoring the number of Treg cells

[80]

β-sitosterol

Anti-inflammatory activity

Inhibition of intracellular adhesion molecule 1 expression in TNF-α-stimulated HAEC as well as the binding of U937 cells to TNF-α-stimulated HAEC and attenuating the phosphorylation of nuclear factor-kB p65

[81]

Cholic acid

Anti-inflammatory activity

Significantly decreasing the content of PGE2 in inflammatory tissue

[82]

Deoxycholic acid

Anti-inflammatory activity

Inhibiting fMLP-induced monocyte and neutrophil chemotaxis and calcium mobilization

[83]

Ursodeoxycholic acid

Anti-inflammatory activity

Ameliorating experimental colonic inflammation in rats at a high dose (50 mg/kg day) by enhancing mucosal defense

[84]

Taurocholic acid

Anti-inflammatory activity

Inhibiting the production of inflammatory mediators, such as NO, PGE2 and histamine

[85]

Others

Bis(7-hydroxyheptyl)decanedioate

Anticoagulative activity

Significant prolongation of thrombin time

[17]

Bis(7-hydroxyheptyl)octanedioate

Protocatechuic acid

Anti-inflammatory and analgesic activities

Significantly decreasing LPO, NO levels and increasing SOD, catalase and GSH levels; significantly increasing the hot pain threshold of experimental mice, and obviously decreasing the frequency of writhing body response

[91]

Hei-Bing-Pian

Steroids

Cholic acid

Anti-inflammatory activity

Significantly decreasing the content of PGE2 in inflammatory tissue

[82]

Taurocholic acid

Anti-inflammatory activity

Inhibiting the production of inflammatory mediators, such as NO, PGE2, and histamine

[85]

Table 4

Basic pharmacological data of commonly used fecal medicines mentioned in the article

Name

Type of extract

Animal or cell

N

Dose

Minimal active concentration

In vitro/In vivo

Positive control

Negative control

Duration

Effect and mechanism

Refs.

Wu-Ling-Zhi

Ethyl acetate extract

Rats

8

15–120 mg/kg

15 mg/kg

In vivo

Ranitidine

Normal saline

12 h

Inhibiting gastric acid secretion and protecting gastric mucosa

[86]

Ethyl acetate extract

Rats

10

200–800 mg/kg

400 mg/kg

In vivo

Aspirin

Normal saline

30 min

Inhibiting the synthesis or release of prostaglandin E (PGE)

[25]

Ethanol extract

MCF-7 cells

5

25–400 μg/ml

100 μg/ml

In vitro

DMSO

24 h

Increasing the expression levels of Caspase 3 and Caspase 9

[29]

Ethyl acetate extract

Rabbits

3

0.62–1.04 mg/ml

0.78 mg/ml

In vitro

Aspirin

DMSO; 60% ethanol; PBS

10 min

Significant prolongation of thrombin time

[87]

Water extract

Rabbits

5

30.8–616 μg/kg

56,225 μg/kg

In vitro

Normal saline

10–15 min

Significant increase of cAMP level in platelets

[88]

Water extract

Rats

7

200–300 mg/kg

200 mg/kg

In vivo

-

Normal saline

20 min

Water extract

Rats

8

20–60 mg/kg

60 mg/kg

In vivo

Ligustrazine

Normal saline

7 days

Significant reduction of MDA and IL1-β levels; increasing SOD activity

[89]

Water extract

Mice and rats

10

5–10 g/kg

5 g/kg

In vivo

Nimodipine

Normal saline

Reducing the brain water content, brain index and MDA level, and increasing SOD activity

[27]

Water extract

Rats

15

2.5–10 g/kg

2.5 g/kg

In vivo

Normal saline

6 week

Down-regulation of the expression of intercellular adhesion molecule-1 in experimental atherosclerotic rats and reducing the degree of vascular endothelial lesions

[28]

Hei-Bing-Pian

Aqueous solution

Rats

8

0.5–2 g/kg

0.5 g/kg

In vivo

Hydrocortisone acetate

10 days

Increasing the expression of SOD and GSH, and reducing the expression of NO and MDA

[40]

Aqueous solution

Rabbits

2

0.01–0.2 g/ml

In vitro

Tyrode’s solution

30 min

Regulating the cholinergic M receptor and histamine receptor

[41]

Rats

6

0.05–0.1 g/kg

In vivo

30 min

Aqueous solution

Rats

8

1–5 g/kg

5 g/kg

In vivo

Domperidone

Normal saline

30 min

Accelerating the rate of gastric emptying, promoting gastrointestinal peristalsis and protecting gastric mucosa

[42]

Mice

10

1–5 g/kg

5 g/kg

In vivo

Domperidone

Normal saline

30 min

Rats

8

1–5 g/kg

5 g/kg

In vivo

Kuai-Wei tablets

Normal saline

15 days

0.5% CMC-Na solution

Rats

20

4–12 g/kg

In vivo

Distilled water

12 w

No toxicity was observed after long-term administration

[43]

Fecal medicines used in other traditional ethnic medicine systems in China

In addition to the TCM system, there are other traditional medical systems in China, such as Tibetan, Mongolian, Uygur, Tujia, Kazak, Yao, Korean, and Dai ethnic medicines. These ethnic medical systems have their own unique theories in the use of natural medicines. Therefore, it is also important to collect information about fecal medicines from these ethnic medical systems.

Traditional Tibetan medicine (TTM) is a representative ethnic medicine in China, and it has a unique fundamental theory, namely three elements theory consisting of “rLung”, “mKhris-pa” and “Badkan” [30]. In TTM system, the use of fecal medicines has a long history. The earliest Tibetan medicine monograph that recorded fecal medicines is “The Four Medical Tantras” [2]. Later, in the seventeenth century, famous “Tibetan Medical Thangka of The Four Medical Tantras” [31] was published by Sde-srid-sangs-rgyas-rgya-mtsho, which vividly depicted some commonly used fecal medicines in the form of wall chart (Fig. 3).
Fig. 3

The Tibetan medical Thangka of “The Four Medical Tantras” vividly depicts some feces medicines and their origin animals (a Tetrao urogallus; b Gallus gallus domesticus; c Pica pica; d Columba livia domestica; e Passer montanus; f Aegypius monachus; g Equus caballus orientalis; h Equus asinus; i Homo sapiens; j Bos taurus domesticus; k Canis lupus; l Sus scrofa; m Canis lupus familiaris; n Rattus rattus; o Lepus oiostolus)

In this study, we found that the feces of 41 animals were used as medicines for the treatment of various diseases in 13 ethnic medical systems. More information on these medicines is provided in Table 2. Among them, the dry feces of Gypaetus barbatus or Aegypius monachus and the processed product of the feces of Sus scrofa are representative fecal medicines in Chinese ethnic medicine systems. Their traditional uses, chemical constituents and pharmacological activities have been described in detail in the following sections.

The dry feces of Gypaetus barbatus or Aegypius monachus (Jiu-Fen in Chinese)

The dry feces of G. barbatus or A. monachus, known as Jiu-Fen in Chinese, is a commonly used Tibetan medicine (Fig. 1d). It has the functions of strengthening stomach and promoting digestion. Jiu-Fen is used in the traditional Tibetan system of medicine for the treatment of dyspepsia, gastrointestinal dysfunction, gastric ulcer, and intestinal cancer in the past few decades [4, 6]. In addition, the “Jing Zhu Materia Medica” recorded that Jiu-Fen can be used to treat mental illness [4]. Nowadays, Jiu-Fen is frequently used in the clinical practice of TTM by combining other herbs. According to our statistics, there are 32 preparations containing Jiu-Fen in some monographs and drug standards of Tibetan medicine [6, 32, 33, 34, 35]. The representative prescriptions include “Shi-Wei-Jiu-Fen Powder”, “Er-Shi-Jiu-Wei-Neng-Xiao Powder” and “Jian-Hua-Mu-Xiang Pills” (Table 5). The “Tibetan Medicine Standards” recorded that “Shi-Wei-Jiu-Fen Powder” can strengthen stomach and promote digestion [6]. Consequently, it is usually used to treat gastrointestinal diseases such as dyspepsia.
Table 5

Representative prescriptions containing fecal medicines recorded in official drug standards

Fecal medicine

Traditional medical system

The number of preparations

The name of prescriptions

Drug standard

Refs.

Wu-Ling-Zhi

TCM

15

Shi-Xiang-Zhi-Tong Pills; Tong-Jing Pills; Shao-Fu-Zhu-Yu Pills; Xiao-Jin Pills; Shi-Er-Wei-Yi-Shou Powder; Er-Shi-Wu-Wei-Song-Shi Pills; Qi-Wei-Tie-Xie Pills; Jiu-Qi-Niao-Tong Pills; Ping-Xiao Pills; Hua-Zheng-Hui-Sheng Tablets; Feng-Liao-Xing-Feng-Shi-Die-Da Wine; Yang-He-Jie-Ning Plaster; Tong-Jing-Bao Granules; Jie-Bai Pills; Bing-Lang-Si-Xiao Pills

Chinese Pharmacopoeia, 2015ed

[7]

Can-Sha

TCM

2

Shu-Jing-Huo-Luo Wine; Feng-Liao-Xing-Feng-Shi-Die-Da Wine

Chinese Pharmacopoeia, 2015ed

[7]

Ye-Ming-Sha

TCM

1

Huang-Lian-Yang-Gan Pills

Chinese Pharmacopoeia, 2015ed

[7]

Jiu-Fen

Tibetan EM

12

Shi-Wei-Jiu-Fen Powder; Er-Shi-Jiu-Wei-Neng-Xiao Powder; Jian-Hua-Mu-Xiang Pills; Shi-San-Wei-Mu-Xiang Pills; Shi-San-Wei-Shi-Liu Pills; De-Ma-Shi-San-Wei-Shi-Liu Pills; Shi-San-Wei-Mu-Xiang Powder; Jia-Wei-Bai-Yao Pills; Qu-Hui Pills; Qu-Han-Quan-Lü Powder; Song-Shi-Da-Peng Pills; Shi-San-Wei-Qing-Lan Pills

Drug Standards of Tibetan Medicines; Tibetan Medicine Standards

[6, 35]

Hei-Bing-Pian

Tibetan EM

14

Shi-Wei-Hei-Bing-Pian Powder; Shi-Yi-Wei-Jin-Se Pills; Shi-Wu-Wei-Zhi-Xie-Mu Powder; Gan-Lu-Ling Pills; Er-shi-Si-Wei-A-Wei Powder; Shi-Yi-Wei-He-Zi Powder; Shi-San-Wei-Di-Da Powder; Niu-Huang-Qing-Peng Pills; He-Zi-Neng-Xiao Pills; He-Zi-Qing Peng-Pills; Jin-Se-Di-Da Pills; Er-shi-Jiu-Wei-Qiang-Huo Powder; Shi-San-Wei-Shu-Tu-Qing-Peng Powder; Shi-Yi-Wei-Jin-Se Powder

Drug Standards of Tibetan Medicines; Tibetan Medicine Standards

[6, 35]

Wu-Ling-Zhi

Mongolian EM

23

Yun-Xiang-Shi-Wu-Wei Pills; Zhi-Li-Shi-Wei-Hei Pills; Niu-Huang-Shi-San-Wei Pills; Wen-Guan-Mu-Shi-Wei Powder; Ji-Xiang-An-Kun Pills; Li-Gan-He-Wei Pills; He-Zi-Wu-Wei Capsules; Bu-Sheng-Jian-Wei-Er-Shi-Yi Pills; Feng-Xiang-Zhi-Shi-Wei Pills; Cao-Guo-Jian-Pi Pills; Ha-Dun-Hai-Lu-Mu-Le-Shi-San-Wei Pills; Ha-Dun-Hai-Lu-Mu-Le-Jiu-Wei Pills; Jian-Wei-Shi-Wei Pills; Jian-Pi-Wu-Wei-Pills; Qing-Gan-Qi-Wei Powder; Tiao-Yuan-Da-Bu-Er-Shi-Wu-Wei Decoction; Ju-Hua-Qi-Wei Capsules; Qing-Gan-Jiu-Wei Powder; Qing-Shen-Re-Shi-Wei Powder; Qing-Wen-Shi-Er-Wei Pills; Qing-Wen-Zhi-Tong-Shi-Si-Wei Pills; Qing-Wen -Li-Dan-Shi-San-Wei Pills; Xi-Hong-Hua-Shi-Liu-Wei Powder

Drug Standards of Mongolian Medicines

[90]

Hei-Bing-Pian

Mongolian EM

7

Zhi-Li-Shi-Wu-Wei Pills; He-Zi-Wu-Wei Capsules; A-Na-Ri-Ba-Wei Powder; Ha-Ri-Shi-Er-Wei Powder; Ha-Dun-Hai-Lu-Mu-Le-Shi-San-Wei Pills; Qing-Gan-Er-Shi-Qi-Wei Pills; Shi-Wei-Hei-Bing-Pian Powder

Drug Standards of Mongolian Medicines

[90]

Ye-Ming-Sha

Mongolian EM

1

Ming-Mu-Shi-Liu Pills

Drug Standards of Mongolian Medicines

[90]

Long-Xian-Xiang

Uygur EM

1

Yi-Mu-Sa-Ke Tablets

Drug Standards of Uygur Medicines

[92]

The use of Jiu-Fen in the traditional Tibetan system of medicine has a long history, but modern research on the chemical composition, quality control and pharmacodynamic evaluation of Jiu-Fen has not yet been carried out. Therefore, further studies are needed to prove its medicinal values in gastrointestinal diseases treatment, identify active compounds and elucidate the underlying mechanisms with the help of modern chemistry and pharmacology methods.

The processed product of the feces of Sus scrofa (Hei-Bing-Pian in Chinese)

The processed product of the feces of Sus scrofa (wild boar), known as Hei-Bing-Pian (Chinese name), is a widely used Tibetan and Mongolian medicine in China (Fig. 1e). Its processing method was recorded in the “Chinese Materia Medica for Tibetan Medicine”: firstly, the dry feces of Sus scrofa is put into a ceramic jar, and yellow mud (adding a small amount of salt) is used to seal the ceramic jar. Secondly, the ceramic jar is calcined with fire until it turns gray outside. Then, the black matter is taken out from the ceramic jar, which is Hei-Bing-Pian [36]. In traditional Tibetan system of medicine, Hei-Bing-Pian is described as pungent in flavor and hot in nature. It is commonly used for the treatment of dyspepsia, gallbladder diseases, stomachache, and plague [6]. According to our statistics, there are 14 Tibetan medicine preparations containing Hei-Bing-Pian in official drug standards. The representative prescriptions include “Shi-Wei-Hei-Bing-Pian Powder”, “Shi-Yi-Wei-Jin-Se Pills” and “Shi-Wu-Wei-Zhi-Xie-Mu Powder” (Table 5). The “Drug Standards of Tibetan Medicines” recorded that “Shi-Wei-Hei-Bing-Pian Pills” is usually used to treat stomach and gallbladder diseases, such as dyspepsia, anorexia, jaundice, gallstones and nausea [35].

It has been reported that Hei-Bing-Pian contains a variety of inorganic elements, such as Fe, Ca, Zn, K, Cu, Mn, Co, Ti, and Mg. At present, the contents of these elements in Hei-Bing-Pian have been determined by using atomic absorption spectrometry or spectrophotometry [37, 38]. The elements with high levels are Ca (18,570 μg/g), K (11,625 μg/g), Mg (9975 μg/g), and Fe (7800 μg/g). Furthermore, two bile acids (i.e., cholic acid and taurocholic acid) were detected and quantified in Hei-Bing-Pian by using ultra high-performance liquid chromatography-mass spectrometry method [21]. Besides, Chang et al. [39] developed a spectrophotometric method to determine the absorption force of Hei-Bing-Pian on tartrazine, and used this adsorption force as an indicator to control the quality of Hei-Bing-Pian.

Modern pharmacological study has demonstrated that Hei-Bing-Pian can prevent mucosal damage caused by experimental colitis in rats. Compared with the model group, the high and low doses of Hei-Bing-Pian can significantly reduce the damage of colonic mucosa congestion, hyperplasia and ulcer (p < 0.05), and significantly increase the levels of superoxide dismutase (SOD) and glutathione (GSH) [40]. Cai et al. [41] reported the effect of Hei-Bing-Pian on the intestinal smooth muscle function of animals. It was found that Hei-Bing-Pian had no obvious effect on normal isolated ileum, and could not antagonize the inhibitory effect of atropine, adrenaline and promethazine on isolated ileum smooth muscle. However, it could significantly inhibit histamine-induced ileal smooth muscle excitation, and the inhibition rate was 25%. Moreover, in vivo studies showed that Hei-Bing-Pian could inhibit the contraction effect of pilocarpine on ileal smooth muscle. These results indicate that the effect of Hei-Bing-Pian on intestinal smooth muscle is related to the cholinergic M receptor and histamine receptor. Bai et al. [42] found that Hei-Bing-Pian could significantly accelerate gastric emptying in rats and promote the propulsive speed of activated carbon in the small intestine of mice. Moreover, the high dose of Hei-Bing-Pian could significantly promote the healing of chronic gastritis caused by acetic acid, and had obvious protective effect on gastric mucosal injury induced by cold stress. Besides, in order to make better use of Hei-Bing-Pian, its long-term toxic effects have been studied by Li et al. The results showed that, after 12 weeks of administration of Hei-Bing-Pian, there were no significant changes in body weight, blood biochemical parameters, histopathology, and several organ indexes (e.g., heart, liver, spleen, kidney, and thymus) in rats, compared with the control group, which indicated that Hei-Bing-Pian has no potential toxicity [43]. The basic pharmacological data of Hei-Bing-Pian and its ingredients are shown in Tables 3 and 4.

Similarities and differences of fecal medicines related to treated diseases in Chinese traditional medical systems

Every traditional medical system in China has its own unique theory or medication experience. Therefore, the same fecal medicines are used in different medical systems, and their therapeutic uses may be different. A detailed comparison of these differences would help researchers and traditional medical practitioners to better understand the indications of fecal medicines and promote their development and utilization. In this study, we compared the similarities and differences of therapeutic uses of Wu-Ling-Zhi and Hei-Bing-Pian in different traditional medical systems, including TCM, Tibetan EM, Korean EM, Dai EM, Yao EM, Tujia EM, Nu EM, and Mongolian EM. Additional details are provided in Table 6. The results indicate that Wu-Ling-Zhi is commonly used to treat amenorrhea and dysmenorrhea in most traditional medical systems. However, its therapeutic uses also have some obvious differences in different medical systems. For example, in the Tibetan EM, Wu-Ling-Zhi can be used to treat stomachache, whereas in the Mongolian EM, it is mainly used to treat diarrhea, gout and itching. Moreover, Wu-Ling-Zhi can treat cold, whooping cough and fever in the Nu EM. Hei-Bing-Pian has the same therapeutic use in TCM and Tibetan EM systems. It is widely used in both systems to treat dyspepsia, biliary diseases, plague and distending pain in the stomach. There is no difference in the therapeutic use of Hei-Bing-Pian in the two medical systems.
Table 6

Similarities and differences of fecal medicines related to treated diseases in Chinese traditional medical systems

Name

Traditional medical system

Original species

Identical indications

Different indications

Refs.

Wu-Ling-Zhi

TCM

Trogopterus xanthipes Milne-Edwards

Amenorrhea and dysmenorrhea

Stabbing pain in the chest and abdomen, swelling and aching due to traumatic injury, and snake bites (external use)

[5, 8, 52]

Tibetan EM

Stomachache

[59, 60]

Korean EM

Stabbing pain in chest and abdomen

[60]

Dai EM

Snake bites (external use)

[60]

Yao EM

Epilepsy

[63]

Tujia EM

Swelling and aching due to traumatic injury, and snake bites (external use)

[60]

Nu EM

Cold, whooping cough and fever

[60]

Mongolian EM

Diarrhea, gout and itching

[62]

Hei-Bing-Pian

Tibetan EM

Sus scrofa L.

Dyspepsia, biliary diseases, plague and distending pain in the stomach

[6, 36, 59]

Mongolian EM

Conclusion and future perspectives

Chinese traditional medicine is an important part of the world’s medical system. In long-term clinical practice, ancient Chinese doctors have accumulated invaluable experience in the use of fecal medicines. As shown in Tables 1 and 2, some fecal medicines have been found to be effective in treating amenorrhea, dysmenorrhea dyspepsia, diarrhea, fever, and stomachache. These traditional medication knowledge are valuable assets. Currently, some fecal medicines (e.g., Wu-Ling-Zhi, Jiu-Fen and Hei-Bing-Pian) are still used in clinical practice. A total of 76 preparations containing fecal medicines were recorded in the latest official drug standards (Table 5). Extensive clinical application demonstrates the role and value of fecal medicines in Chinese medical systems. Moreover, Wu-Ling-Zhi extracts and its chemical constituents have been proved to possess a wide spectrum of biological activities, such as anti-inflammatory, anticoagulative and antioxidant effects (Tables 3 and 4). Some possible molecular mechanisms have also been revealed. The results of these modern pharmacological studies provide some evidences to prove the scientific nature of fecal medicines. However, most fecal medicines still lack experimental evidences. For example, Jiu-Fen is a commonly used Tibetan medicine. However, so far, no biological activities or active ingredients have been reported for this drug. Therefore, in order to better develop and utilize these fecal medicines, more in vivo pharmacological studies and even clinical evaluations should be performed to prove their scientific and medicinal value.

Fortunately, an in-depth study of gut microbiota has provided an opportunity to interpret the scientific connotation of some traditional fecal medicines, such as the yellow soup. This soup is a fresh fecal suspension of Homo sapiens commonly used to treat food poisoning, severe diarrhea, heat toxins, and unconsciousness due to high fever. Zhang et al. [44, 45] believe that the efficacy of yellow soup is mainly caused by the gut microbiota from fresh fecal water, and its principle for treating diseases is similar to the fecal microbiota transplantation method of modern medicine. Therefore, reconstructing the gut microbiota of patients may be the mechanism of action of fresh fecal medicines for treating diseases.

However, most fecal medicines are derived from dry feces (e.g., Wu-Ling-Zhi) or processed products (e.g., Hei-Bing-Pian). During drying and processing, these fecal medicines lose the living microbiota. Therefore, their mechanisms for treating diseases may be different from fresh feces. Feces are intestinal excretions of humans or animals. The chemical constituents in feces are mainly derived from the host or dietary metabolites. These metabolites may be the key active constituents of fecal medicinal materials. For example, the terpenoids, flavonoids and lignans contained in Wu-Ling-Zhi are closely related to the foods eaten by Trogopterus xanthipes (e.g., Platycladus orientalis leaves, Pinus tabulaeformis bark, and peach kernels). These diet-derived metabolites may be the pharmacologically active ingredients of Wu-Ling-Zhi. Moreover, some bile acids (e.g., deoxycholic acid, lithocholic acid and taurocholic acid) have been found in Wu-Ling-Zhi and Hei-Bing-Pian [21]. These bile acids are the final metabolites of cholesterol under the common metabolism of liver and gut microbiota. Bile acids are endocrine-signaling molecules that regulate metabolic processes, including glucose, lipid and energy homeostasis, by regulating gut microbiota or activating bile acid receptors, such as the farnesoid X receptor (FXR) and G protein-coupled bile acid receptor 1 [46, 47, 48]. Distrutti et al. [49] reported that bile acids-activated receptors are targets for maintaining intestinal integrity. Gadaleta et al. [50] found that FXR activation could prevent chemically induced intestinal inflammation with an improvement of colitis symptoms and inhibition of epithelial permeability. In addition, bile acids can also regulate cardiovascular functions via receptor-dependent and -independent mechanisms [51]. These findings provide a rationale to explore the mechanisms of Hei-Bing-Pian and Wu-Ling-Zhi in the treatment of gastrointestinal and cardiovascular diseases, respectively.

With the continuous development of science and technology, some unique but sometimes incomprehensible drugs in traditional medical systems will gradually be recognized. In this study, we provide the first comprehensive data compilation of fecal medicines used in Chinese traditional medical systems. The information recorded in ancient monographs and drug standards, such as original species, traditional uses and indications, can provide a good reference for the development and utilization of fecal medicines. In view of the current research status of fecal medicines, future research may focus on the following aspects: (1) applying multidisciplinary methods to further prove their effectiveness and medicinal value, (2) revealing their active ingredients associated with clinical efficacy using phytochemical and pharmacodynamic methods, and (3) elucidating the mechanisms of action of fecal medicines based on gut microbiota or receptor-mediated signaling pathways.

Notes

Acknowledgements

Not applicable.

Authors’ contributions

HD, T-TK: conducted the research, collected the data, and wrote the paper; SQ, TX: collected, organized, and analyzed the data; C-L GH: collected the Tibetan fecal medicines; and YZ, GF: conceived and designed the study. All authors read and approved the final manuscript.

Funding

This research was support by the National Key Research and Development Program of China (No. 2017YFC1703900) and National Natural Science Foundation of China (No. 81874370).

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

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Authors and Affiliations

  1. 1.School of PharmacyChengdu University of Traditional Chinese MedicineChengduChina
  2. 2.School of Ethnic MedicineChengdu University of Traditional Chinese MedicineChengduChina
  3. 3.School of Foreign LanguageChengdu University of Traditional Chinese MedicineChengduChina

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