Peucedanum L. (Umbelliferae) consists of 120 species of herbaceous perennial plants which are distributed widely across the globe (Editorial Committee of Flora of China, 1992). One member of the genus, Peucedanum praeruptorum Dunn, is cultivated in montane habitats at an altitude between 250 and 2000 m. In traditional Chinese medicine (TCM), the root tissues of P. praeruptorum (Qianhu) have been utilized for hundreds of years to address diverse respiratory ailments, including cough, asthma, and pulmonary hypertension (Zhou et al., 2013). The roots of P. praeruptorum demonstrate diverse pharmacological activities, including anti-inflammatory, neuroprotective, antitumor, anti-osteoclastogenic, antidepressant, and osteogenic effects (Song et al., 2022). In addition, P. praeruptorum has been found to contain an array of useful phytochemicals, including simple coumarins, pyranocoumarins, furanocoumarins, flavonoids, ketones, sterols, and organic acids, and others (Song et al., 2022).

However, to date, there has been no comprehensive and systematic evaluation of the bioactivities, pharmacology, structures, functions, and toxicities of these phytochemicals, or of P. praeruptorum crude extracts. Moreover, the traditional uses of P. praeruptorum and their pharmacological evidence have not been critically evaluated. Here, we systematically summarized the toxicology, molecular mechanisms, pharmacology, phytochemistry, botany, quality control, and traditional uses of P. praeruptorum to validate the medicinal use of this species. To further clarify the material basis of P. praeruptorum’s medicinal effect, identifying the structures of metabolites will provide a certain theoretical basis for the further development and utilization of Qianhu. The information presented here can aid the planning of clinical trials and the development of novel medicines containing P. praeruptorum or its active constituents.

Information pertaining to P. praeruptorum was sourced from scientific databases (ScienceDirect, Web of Science, Springer, Google Scholar, SciFinder, PubMed, Baidu Scholar), as well as toxicology papers from local conferences, M. Sc. and Ph.D. theses and dissertations, local magazines, classic texts on Chinese botanical drugs, and peer-reviewed journals. We utilized the following, as well as related, keywords to perform the literature review: P. praeruptorum Dunn, secondary metabolites, toxicology, safety, ethnobotanical survey, quality control, pharmacology, medicinal uses, phytochemistry, and biological activity. The Plant List (www.theplantlist.org) was utilized to verify the taxonomy of P. praeruptorum and verify subspecies and cultivars. The chemical structures were drawn using ChemDraw.

P. praeruptorum Dunn (Figure 1) is an herbaceous perennial in the Umbelliferae family. P. praeruptorum Dunn is the only accepted name for the species (www.theplantlist.org), although it has two other synonyms: P. praeruptorum var. grande K.T. Fu and P. praeruptorum subsp. hirsutiusculum Ma. P. praeruptorum is found in the wild in south China, including in Zhejiang, Anhui, Jiangxi, Hubei, Hunan, Guizhou, Sichuan, and Yunnan provinces (Figure 2). The traditional production areas are northwest Zhejiang, southeast Anhui, and northeast Jiangxi, where the plant is called “Zhe Qianhu,” “Ning Qianhu,” and “Xin Qianhu,” respectively (Zhou et al., 2021).

According to the Flora of China (Editorial Committee of Flora of China, 1992), P. praeruptorum grows along forest edges, near roadsides, and in semi-open grassy areas within montane habitats at an altitude of 250–2000 m (Liu et al., 2021). P. praeruptorum can reach a height of 60–100 cm. The plant has a cylindrical stem, with a glabrous lower part and piliferous branches on the upper part. The medulla is solid. Leaves are wide ovate or triangular ovate. The compound umbel is terminal or lateral, and 3.5–9 cm in diameter. The fruits are oval, 4 mm in length and 3 mm in width. The back of the fruit is flat. The rhizomes are strong, brown, and 1–1.5 cm in diameter. The roots are conical and branched, with thin root ends. For medicinal use, roots are collected from winter to spring. Abluent, fresh, thin slices are dried prior to medicinal use.

The List of Mingyi Bielu (《名医别录》), which dates to the Wei-Jin and South-North Dynasties (A.D. 220-450), was the first to record the roots of P. praeruptorum as TCM. Many ancient texts, such as the Rihuazi Bencao (《日华子本草》) (Five Dynasties, A.D. 908–923), the Compendium of Materia Medica (《本草纲目》) (Ming Dynasty, A.D. 1578), and the Illustrated Classics of Materia Medica (《本草图经》) (Song Dynasty, A.D. 1061) also record that P. praeruptorum was widely used to treat colds, headaches, coughs, asthma, and chest congestion (He et al., 2007). In the Chinese Pharmacopoeia 2000 (Chinese Pharmacopoeia Committee of People’s Repulic of China, 2000), Qianhu is defined as the roots of either P. decursivum (Miq.) Maxim (Zihuaqianhu) or P. praeruptorum Dunn. However, P. decursivum is not traditionally used as a source of Qianhu, and thus, was removed from the Chinese Pharmacopoeia 2005 (Chinese Pharmacopoeia Committee of People’s Repulic of China, 2005). More recently, the Chinese Pharmacopoeia 2010, 2015, and 2020 (Chinese Pharmacopoeia Committee of People’s Repulic of China, 2010; Chinese Pharmacopoeia Committee of People’s Repulic of China, 2015; Chinese Pharmacopoeia Committee of People’s Repulic of China, 2020) define Qianhu as the roots of P. praeruptorum exclusively, while Zihuaqianhu is defined as the roots of P. decursivum.

P. praeruptorum has many folk names, including yimacai, luoguicai, shuiqianhu, shuifangfeng, shanyuansui, guanqianhu, and shanduhuo. In TCM, Qianhu is used to treat chronic respiratory failure, acute bronchitis, and iridocyclitis after cataract surgery (Wang, 2016). The roots of P. praeruptorum have been utilized in a variety of traditional preparations, and are often used in combination with Mentha haplocalyx Briq., Arctium lappa L., and Platycodon grandiflorum (Jacq.) A. DC. to treat external wind-heat, body heat, headache, cough, and phlegm. In addition, P. praeruptorum is used in combination with Citrus reticulata Blanco, Pinellia ternata (Thunb.) Breit., and Prunus armeniaca L. var. ansu Maxim. to treat cough, chest congestion, vomiting, and nausea. The roots of P. praeruptorum have been used in more than 189 TCM preparations and 525 classical prescriptions (https://db.yaozh.com, accessed 7th December, 2023). Examples of TCM prescriptions containing P. praeruptorum are listed in Table 1. “Bai He Qian Hu Tang,” “Da Qian Hu Tang,” “Fu Ling Qian Hu Tang,” “Jiu Wei Qian Hu Tang,” and “Xing Su San” are Chinese classical prescriptions recorded in many ancient books. The botanical drugs “Tong Xuan Li Fei Ke Li” and “Tong Xuan Li Fei Pian” (Chinese Pharmacopoeia Committee of People’s Repulic of China, 2020), which are accredited by the National Medical Products Administration, are produced and marketed in China to treat cough. However, further research is required to clarify any potential synergisms or interactions between the bioactive phytochemicals in P. praeruptorum and those of other medicinal plants, as well as to elucidate their mechanisms of action. According to the Chinese Pharmacopoeia 2020 (Chinese Pharmacopoeia Committee of People’s Repulic of China, 2020), although Qianhu can disperse wind-heat, reduce cough and phlegm, and dissipate adverse Qi, comprehensive studies of its constitutive bioactive monomers should be conducted.

P. praeruptorum is reported to contain a diverse array of phytochemicals, including simple coumarins (1–13), pyranocoumarins (14–66), furanocoumarins (67–94), ketones (95, 96), sterols (97, 98), and organic acids (99–105), and others (106–119) (Table 2). The majority of these phytochemicals were isolated from root tissues, which are the traditional medicinal material. Among these isolated metabolites, angular pyranocoumarins (e.g., praeruptorins A and B) are the most abundant bioactive metabolites in P. praeruptorum tissues (Song et al., 2015).

P. praeruptorum exhibits diverse pharmacological activities (Table 3), including anti-inflammatory, expectorant, antitussive, antitumor, neuroprotective, anti-osteoclastogenic, and antidepressant effects. The antitumor, immunoregulatory, and anti-inflammatory activities are the most notable, and putative molecular mechanisms are shown in Figure 8.

Praeruptorins A, B, and C, the primary metabolites of P. praeruptorum, exhibit diverse biological activities, including neuroprotective, antitumor, anti-inflammatory, immunoregulatory, anti-osteoclastogenic, and antidepressant effects. Recently, researchers developed a liquid chromatography–selected ion monitoring–mass spectrometry (LC–SIM–MS) method to conduct a pharmacokinetic study of WaiGan KeSou Formula decoction administered to rats at a dose of 20 mL. The monarch drug of WaiGan KeSou Formula was Qianhu, and its index compound was Praeruptorin A. Within 24 h, the peak concentration (C_max) of praeruptorin A in plasma was 172.697 ± 17.254 ng/mL, the peak time was 1.50 h, the elimination half-life (t_1/2) was 1.02 h, the mean retention time was 3.42 h, the AUC_0–τ (area under the curve) was 504.866 ± 50.317 h ng/mL, and the AUC_0–∞ was 514.401 ± 36.950 h ng/mL (He and Wu, 2021). In addition, LC-MS/MS was utilized to evaluate the plasma concentrations of praeruptorin A in rats after a single intragastric dose of 8 g/kg body weight. The researchers found that praeruptorin A was detectable up to 24 h after administration, with an AUC_0–t of 311.80 ± 42.38 ng h/mL, a C_max of 31.09 ± 4.84 ng/mL, and a t_1/2 of 7.52 ± 1.00 h (Zhou et al., 2015).

A sensitive, selective, and rapid online solid phase extraction-chiral LC–MS/MS method was developed to conduct a pharmacokinetic study of praeruptorins B and C after orally administering P. praeruptorum extract to rats. Praeruptorins B and C were detectable in rat plasma up to 24 h after administration, with AUC_0–t values of 187.29 ± 15.02 (B) and 91.64 ± 9.37 h ng/mL (C), C_max values of 19.66 ± 4.25 (B) and 7.59 ± 1.98 ng/mL (C), and t_1/2 values of 8.20 ± 1.21 h (B) and 14.97 ± 3.66 h (C) (Zhou et al., 2015). Nonetheless, additional pharmacokinetic studies should be conducted on the other bioactive metabolites present in P. praeruptorum, including praeruptorin D, praeruptorin E, qianhucoumarin B, and praeroside I.

Qianhu is typically processed by washing and immediately drying at low temperature, which must be kept below 60°C. Fresh slices should be thicker than 6 mm (Ren et al., 2021). To maintain medicinal quality, the Chinese Pharmacopoeia dictates the use of microscopic, morphological, HPLC, and TLC detection and identification, as well as ethanol extraction and cold-dipping. By utilizing cold-dipping, the ethanol extract must be more than 20.0% for P. praeruptorum. According to the requirements of the Chinese Pharmacopoeia (Chinese Pharmacopoeia Committee of People’s Repulic of China, 2020), the moisture content (after drying) must not exceed 12.0% and the ash content must not exceed 8.0%. Moreover, different extraction methods have different effects on the index metabolites of P. praeruptorum (praeruptorins A and B). The reflux method is favored for the extraction of praeruptorin A, producing a much higher praeruptorin A content than ultrasonic methods. Conversely, the ultrasonic method is favored for the extraction of praeruptorin B, producing a much higher praeruptorin B content than the reflux method (Xu et al., 2022). However, it is inadvisable to utilize only one crude, quantitative marker when assessing the quality of P. praeruptorum extracts. An array of bioactive metabolites has been detected in P. praeruptorum by HPLC, UV, gas chromatography (GC), NMR, high-speed counter-current chromatography coupled with electrospray ionization multi-stage MS (prep-HSCCC/ESI-MS(n)) (Zhou et al., 2015).

The medicinal quality of P. praeruptorum is affected by the altitude at which it is produced. According to reports by Luo et al. (2022), an altitude of 900 m improved the praeruptorin A content, while an altitude of 650 m improved the praeruptorin B content. Moreover, the influence of altitude was greater on praeruptorin B content than on praeruptorin A content (Luo et al., 2022). In another study, praeruptorin A and B contents were higher in plants cultivated at high altitudes than in plants cultivated at low altitudes by using HPLC-DAD method to determine the contents of praeruptorin A and B in the 24 batches of Qianhu from different producing areas. According to the experimental results, cluster analysis and principal component analysis were carried out (Yang et al., 2021). In addition, the key climatic factors affecting the praeruptorin content are average relative humidity, average maximum temperature in July, average annual temperature, and average temperature in July (Xu et al., 2021). However, the relationships between Qianhu quality and climatic factors have not been widely investigated, and warrant further study.

Praeruptorin A and B contents are also influenced by plant organ, harvesting time, cultivation environment, and fertilization strategy. According to reports by Li et al. (2022), the HPLC method was used to determine the content of praeruptorin A and B in the cultured P. praeruptorum at different harvesting periods, as well as to analyze the fluctuation of praeruptorin A and B at different harvesting periods. Praeruptorin A and B contents are highest in P. praeruptorum roots, followed by stems, and are lowest in leaves. In the 14 samples, the praeruptorin A content was found to be much higher in 2-year-old P. praeruptorum than in 1-year-old P. praeruptorum. Moreover, plants cultivated on southern slopes exhibited an approximately 80% higher content of praeruptorin A than plants grown on slopes of other orientations. However, no significant differences in the contents of praeruptorin A or B were observed in P. praeruptorum harvested before or after bolting (Li et al., 2022). Finally, the reasonable application of P and K fertilizers has been found to improve both the yield and medicinal quality P. praeruptorum, although the application of N fertilizer should be controlled (Zhou et al., 2022).

Praeruptorin C exerted no toxicity on primary cultures of mouse neurons at doses of 0 and 10 μg/mol (Yang et al., 2013). Moreover, an emulsion of praeruptorin C did not exert any toxicity or induce any behavioral changes at doses of 5 and 40 μg/mol in OVX mice by performing a CCK-8 assay (Liu et al., 2017). In BMMs, praeruptorin A was found to be atoxic at doses under 10 mmol/L, but significantly cytotoxic at doses over 20 mmol/L (Yeon et al., 2014). In HepG2 cells, praeruptorins A and C were found to be atoxic at doses of 10 and 100 μg/mol, respectively (Zhou et al., 2013). However, a maximum dose of 200 μg/mol dramatically increased cell toxicity. The toxicity of praeruptorin B on SK-OV-3 ovarian cancer cells was not obvious at doses of 20 and 60 μmol/L (Xue et al., 2021). HCC cell line and normal liver THLE-2 cells were treated with different concentrations of praeruptorin A (0, 10, 20, 30, 40 μg/mL) for 24 h. The cell viability was assessed through 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide assay. The results implied that praeruptorin A did not induce cytotoxicity in an HCC cell line at doses of 10 and 40 μg/mL (Yu et al., 2021). In addition, praeruptorin A was atoxic to normal liver THLE-2 cells under at concentrations of 10–30 μg/mol. The Chinese Pharmacopoeia 2020 (Chinese Pharmacopoeia Committee of People’s Repulic of China, 2020) recommends a Qianhu dosage of 3–10 g/d. In addition, Qianhu can safely be used with Pinelliae Rhizoma, but not with Gleditsia sinensis Lam. or Veratrum nigrum L. (“Bencaojing Jizhu” 《本草经集注》). Finally, Qianhu is not considered suitable for people with Yin deficiency syndrome (a series of symptoms caused by the deficiency of yin essence or fluid in the human body. Yin: the dark, not active, female principle of the Universe in Chinese philosophy) (Wen, 2023), cough, cold, or cold fluid syndrome. According to cell studies, P. praeruptorum appears to be atoxic at a low dose but cytotoxic at higher doses (Zhou et al., 2013; Yeon et al., 2014).

P. praeruptorum is a classical medicinal plant commonly used in TCM preparations. Here, we systematically evaluated the toxicology, molecular mechanisms, pharmacology, phytochemistry, botany, quality control, and traditional uses of P. praeruptorum in order to validate the medicinal use of this species. According to the Chinese Pharmacopoeia and classical Chinese botanical drugs, P. praeruptorum has been historically prescribed to treat a wide spectrum of diseases including cough, asthma, and pulmonary hypertension. Pharmacological studies suggest that P. praeruptorum exhibits anti-inflammatory, expectorant, antitussive, antitumor, neuroprotective, anti-osteoclastogenic, and antidepressant effects, and largely support the traditional uses of this plant. To date, more than 119 distinct phytochemicals have been identified in P. praeruptorum extracts, the most common of which are pyranocoumarins and furanocoumarins.

Although there has been considerable progress in evaluating the phytochemistry and pharmacology of P. praeruptorum, there are still gaps in our knowledge. First, according to the Chinese Pharmacopoeia 2020 (Chinese Pharmacopoeia Committee of People’s Repulic of China, 2020), Qianhu can disperse wind-heat, reduce cough and phlegm, and dissipate adverse Qi, indicating that Qianhu may alleviate the effects of wind-heat on the lungs (Song et al., 2015). However, most of the active metabolites of P. praeruptorum effective against cough and wind-heat are currently administered as crude extracts. Therefore, comprehensive investigations should be conducted to identify the effective metabolites and elucidate their modes of action in order to facilitate clinical trials. Second, we found few reports on the toxicity of P. praeruptorum extracts or potential botanical drugs interactions. The potential adverse effects, contraindications, and toxicities of P. praeruptorum extracts and their bioactive metabolites should therefore be studied in vitro, in vivo, and in clinical trials. Third, the majority of the reviewed research was conducted in cell cultures or animal models. Clinical trials in humans will be required to truly evaluate the efficacy P. praeruptorum in addressing depression, osteoporosis, cancer, and inflammation, among other diseases. Forth, most of the P. praeruptorum containing health products are mainly derived from its root rich in chemical compounds, while non-medicinal parts are rarely exploited. Therefore, it may be interesting to extend the research to the non-medicinal parts of the inexpensive flowers, leaves, and stems of P. praeruptorum to ensure the fully utilization of its edible and medicinal values. Finally, new and updated analytical and quality control methods will be required to identify novel markers of quality for the assessment of TCM preparations.

In conclusion, P. praeruptorum is rich in medicinal materials, and its pharmacological effects are extensive. With the advantages of modern instruments and data analysis technology in identifying chemical components and separation, Qianhu medicinal materials can be better developed and new drug discovery (Liu, 2020). Future research should be conducted to investigate the mode of action responsible for the pharmacological activities of P. praeruptorum extracts, as well as to comprehensively evaluate the potential toxicities, adverse effects, and contraindications of this botanical drugs. Alongside updated quality control measures, these investigations will facilitate clinical trials. Updated in vivo pharmacological studies must be performed to validate the traditional uses of P. praeruptorum. Finally, the clinical safety and efficacy of P. praeruptorum-derived phytochemicals in the treatment of depression, osteoporosis, cancer, and other diseases, require validation.