Toxicological Advances Of Traditional Medicine in 2019

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Highlights

The paper reviewed research concerning the toxicology of traditional medicine(Traditional Medicine)and active natural products during the past 12 months, and find that liver, kidney, and heart are the main toxic target organs of traditional Medicine. In addition. drug safety for the maternal and child began to be focused on in 2019. and safety assessment of Aconitum Carmichael Debx, Tripterygium Wilford Hook.f, Srychnos nux-vomica L, Fallopia multiflora (Thumb.) Harald, etc. is still a hot issue.

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Traditionality

This annual review summarized the new toxicology study technology, common evaluated models toxic target organs, safety evaluation of Traditional Medicine in different kinds of people, and popular research issues and herbs in 2019. Compared to 2018, many counties like Australia, Germany, and the UK start to pay attention to the safety evaluation of Traditional Medicine.

Toxicological advances of traditional medicine in 2019

Abstract

There were many types of research concerning the toxicology of traditional medicine and active natural products during the past 12 months. This annual toxicology review summarized target organs of Traditional Medicine like the liver, kidney, and heart. Safety medication of Traditional Medicine has been concerned to different kinds of people, including infants, children, pregnancy and the postnatal period, Besides rodents. zebrafish embryos have been regarded as common models to evaluate the safety of Traditional Medicine. New technologies in toxicology focus on rapidly screening and identification of toxins in Traditional Medicine. Multispectral optoacoustic tomography imaging the precise location of Traditional Medicine-induced liver injury with 3D information and integrating serum exosomal microRNA and liver microRNA profiles are used to explain the mechanism of Traditional Medicine-induced hepatotoxicity. Taken together, studies on the toxicity mechanism of other target organs, drug safety in elders, new models, and methods should be paid attention to in the prevention of Traditional Medicine toxicology in the future.

Keywords: Traditional medicine, Natural product, Herb, Toxicity, Toxic target organs, Risk assessment, Safety evaluation

Background

Safety, effectiveness, and quality control belong to three basic characteristics of drugs. In 2019, there were a number of papers that referred to the safety assessment of toxins [1] like metal [2], elemental distribution [3], toxic proteins [4, 5], and special secondary metabolites in traditional medicine (Traditional Medicine), which might be also the bioactivation of herbal constituents [6]. The herbs included Cuscuta Chinensis Lam epithelium [7], Cassiae semen [8], Ephedra sinica Stapf [9], Melia to send Sieb.et Zucc.[10], Psoralea corylifolia Linn.[11], Gymura segetum(Lour)Merr [12],Leomurus aremisia (Laur)S.Y. Hu F [13]。Polygonum multiflorum [14-16], Tripterygium Wilford Hook. f. [17,18], Telfaria occidentalis root [19,20], and so forth. At the same time, people paid attention to different age groups such as infants [2], children [21-23], adults [24], pregnancy, and the postnatal period [13,25-27] in the use of Traditional Medicine. Liquid Chinese patent drugs, especial for injection received researchers more attention like Xiyanping injection [28], Tianfoshen oral liquid [29], and motherwort injection [13]. New detection technology like multispectral optoacoustic tomography (MSOT)imaging the location 1of precise herbal-medicine-induced liver injury with 3D information in a non-invasive way using conjugated-polymer-based ratiometric nanoprobe was applied [14]. A computational toxicology approach was also applied to screening the hepatotoxic ingredients in Traditional Medicine[15]. Furthermore, China played a key role in the promotion of the rapid upsurge in this field. Statistical analysis of annual publications of toxicological studies on Traditional Medicine by relative percentages in different countries is shown in Figure 1. The USA ranked the second important country, while India was tied with Canada and Brazil ranked the third place researching the toxicology of Traditional Medicine. In addition, compared to 2018, many counties like Australia, Germany, and the UK started to pay attention to the safety evaluation of Traditional Medicine.

Organ toxicity

The liver is regarded as the top 1 toxic target organ in TV

The liver is the most important organ of drug metabolism and detoxification in the body. For herb-induced liver injury was a growing clinical and economic problem worldwide, there were a large number of researches focusing on liver toxicity in 2019. For example, new detection technologies like MSOT imaging the precise location of Fallopia multiflora (Thunb.)Harald-induced liver injury with 3D information was applied due to oxidative/nitrosative stress resulting in fromhepaticall-generated reactive oxygen species/reactive nitrogen species [14]. A computational toxicology approach was applied to screening the hepatotoxic ingredients in Fallopia multiflora(Thunb.)Harald [15]. Integrating serum exosomal microRNA and liver microRNA profiles were used to disclose the mechanism of Melia toosendam Sieb.et Zucc.-induced hepatotoxicity in mice [10]. Meanwhile, metabolism was used commonly to display cholestatic liver injury caused by psoralen 30,isopsoralen 30]and Gvura segetum(Louar:)[12], and metabolic disorders like glycerophospholipid metabolism, primary bile acid biosynthesis, sphingolipid metabolism, phenylalanine, tyrosine, and tryptophan biosynthesis, and tyrosine metabolism by Daphne genkan Sieb. et Zucc.[31]Ghycyrrhia uralensis Fisch.[31], Sophora flavescens Ait. [32] and Xysmalobium undulatum [33].

The kidney is considered as the second toxic target organ in Traditional Medicine

Renal blood flow is abundant, accounting for 25% of cardiac output, so a large number of drugs can reach the kidney with blood flow to cause pathological changes. For example, aristolochic acid I was recognized as the major cause of aristolochic acid nephropathy before [34]. During 2019, untargeted liquid chromatograph-mass-spectrometer-based metabonomics was used to reveal that aristolochic acid I inhibited amino acids metabolism, glucose metabolism, beta-oxidation of fatty acids, and the tricarboxylic acid cycle in male mice [35]. Aristolochic acid I could also react with genomic DNA to form persistent DNA adducts with purines to induce nephrotoxicity [36]. Chemotherapy usually induced nephrotoxicity like cisplatin [37| and doxorubicin [38]. In the year 2019, researchers reported that grape pomace extract did not protect against cisplatin-induced nephrotoxicity, but accentuated the toxic effect of cisplatin [37]. Dioscorea bulbifera L. delayed the excretion of doxorubicin and accumulated doxorubicin in the body, which was associated with its inhibition of P-glycoprotein in the liver and kidneys [38]. Furthermore, it was reported that the incompatible herb pair Euphorbia kansui T. N.Liou ex S. B. Ho and Glycyrrhiza uralensis Fisch. induced hepatotoxicity and nephrotoxicity and attenuated the effect of Gansui Banxia decoction [39].

Other toxic target organs of Traditional Medicine

In 2019, a review introduced poisoning by toxic plants in Hong Kong. 62 cases involving 26 poisonous plant species were identified, among which Alocasia mycorrhizas(Giant Alocasia), Gelsemium elegans (Graceful Jessamine), and Rhododendron (Azalea)species were the three most commonly encountered. Gastrointestinal toxicity(n = 30,48%), neurological toxicity(n= 22,35%),and hepatotoxicity (n =6.10%)were the three most common clinical problems. Forty-nine (79%)and eight(13%)patients had mild and moderate toxicity, respectively. They were all recovered shortly with supportive treatment in Traditional Medicine. The remaining five(8%) patients experienced severe toxicity requiring intensive care support [40].

Meanwhile, the mechanisms of reproductive injuries induced by a combination of Daphne genkwa Sieb. et Zucc. and Glycyrrhiza uralensis Fisch. [31], cardiotoxicity and neurotoxicity caused by diester and monoester diterpenoid alkaloids in processed Aconitum Carmichael Debx. root [41], cardiotoxicity induced by Chloranthus serratus [42], a gastrointestinal injury incurred by Gardenia jasminoides Ellis [43], and so forth were explained in 2019. These extracts should be used with caution. Taken together, statistical analysis of annual publication referred to different toxic target organs induced by Traditional Medicine is summarized in Figure 2.

Figure 1 Statistical analysis of annual publications on toxicological studies on Traditional Medicine by relative percentages in different countries. Traditional Medicine

Figure 2 Statistical analyses of annual publications on toxicological studies on Traditional Medicine by relative percentages on different toxic target organs. Traditional Medicine

Current advances

Zebrafish embryos are popular for evaluating the safety of Traditional Medicine

Right now, the safety evaluation has been applied at cellular, organ & individual levels. Rodents are regarded as the common individual models to analyze the safety of Traditional Medicine or natural products. Meanwhile, zebrafish embryos are secondly widely used because of their rapid, medium-throughput, and cost-effectiveness. In 2019, it was used to evaluate the liver protection and hepatotoxicity of saikosaponin a [44], aloe-emodin [45], and triptolide [46], teratogenicity of Momordica charantia seeds and fruits [47], heart toxicity of Libidibia ferret (juca) [48], reproductive toxicity of Endopleura Uchi (Huber) Cuatrec [49] and so forth. Although Caenorhabditis elegans [50] and drosophila [51] were popular in the safety evaluation of various chemical compounds recently, there was no relative research in Traditional Medicine in 2019.

Safety evaluation of Traditional Medicine in different kinds of people

Recently, safety medication has been concerned to different kinds of people, such as infants [2], children [21–23], adults [24], and maternal [13, 25–27]. In 2019, a review reported the safety of the herbal medicinal product used during pregnancy and postnatal periods [25]. In this report, almond oil might induce preterm birth, the use of oral raspberry leaf was related to cesarean delivery; the application of heavy licorice use was relative to early preterm birth by 3.07-fold. African herbal medicine mwanaphepo was also reported to be associated with maternal morbidity, neonatal death, or morbidity [25]. Meanwhile, other researchers reported that Anastatica hierochuntica aqueous extract [26] and Snus tobacco [27] displayed potential toxicity during pregnancy. What’s more, it attracted attention to the safety assessment of toxic metals in commonly used pharmaceutical herbal products in the Jordanian market [2], a mixed extract containing marshmallow root, chamomile flowers, horsetail herb, walnut leaves, yarrow herb, oak bark, and dandelion herb in the area traditional Medicine of acute non-bacterial tonsillitis [21], and green tea [22] in children.

New toxicology study technology

In 2019, new technology was used in toxicology evaluation. For example, a computational toxicology approach was also applied to screening the hepatotoxic ingredients in Traditional Medicine [15]. Electrospray laser desorption ionization mass spectrometry was used to rapidly identify herbal toxins [1]. MSOT imaging conjugated with polymer-based ratiometric nanoprobe was applied for the precise location of Traditional Medicine-induced liver injury with 3D information in a noninvasive way [14]. Furthermore, integrating serum exosomal microRNA and liver microRNA profiles were used to disclose the mechanism of Traditional Medicine-induced hepatotoxicity in mice [10].

Conclusion

Taken together, the annual research shows that the liver, kidney, and heart are the main toxic target organs of Traditional Medicine. Their toxic mechanisms include cell apoptosis, metabolic disorder, oxidative stress, inflammatory damage, liver and renal fibrosis and even inducing carcinogenesis. Safety medication of Traditional Medicine has been a concern to different kinds of people, such as infants. children and maternal. Besides rodents, zebrafish embryos have been regarded as common models to evaluate the safety of Traditional Medicine. New technologies in toxicology focus on how to screen and identify toxins in Traditional Medicine, how to image the precise location of Traditional Medicine-induced tissue injury with 3D information, and how to explain the mechanism of Traditional Medicine-induced toxicity. In the future, study on the toxicity mechanism of other target organs, drug safety in elders, new models and methods should be used in the prevention of Traditional Medicine toxicology.

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