Mexican Medicinal Plants: History
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Subjects: Pharmacology & Pharmacy
Contributor:
Geovanna Quiñonez-Bastidas

Some natural compounds belonging to the group of Mexican medicinal plants or “Mexican folk medicine”are  used for pain management in Mexico.

  • neuropathic pain
  • inflammatory pain
  • chronic pain
  • natural compounds
  • Mexican plants
  • pain treatment

1. Introduction

According to the International Association for the Study of Pain (IASP), inflammatory and neuropathic pain are unpleasant and incapacitant conditions that impair the quality of life of those who suffer from that condition. The pathological origins of inflammatory and neuropathic pain are different—inflammatory pain is produced by a lesion in tissue [1], whereas neuropathic pain is a consequence of a lesion or disease affecting the somatosensory system [2][3]. Both inflammatory and neuropathic conditions are commonly represented as chronic pain when the pain lasts or recurs for longer than 3 months [4]. In this way, chronic pain is considered a big problem for the politics of health in developing and developed countries [5]. The prevalence of moderate–severely disabling chronic pain has been estimated to be between 10.4% to 14.3% [6].

A large number of anti-pain drugs for inflammatory and neuropathic conditions have been developed and fully tested in clinical studies [7][8]. The currently pharmacological treatment is usually classified according to the class of pain; moreover, some combinations have been probed to create a synergistic analgesic effect and reduce side effects exhibited by anti-pain drugs [8]. In this regard, NSAIDs such as naproxen, ibuprofen, ketorolac, and some selective COX-2 inhibitors, have side effects on the cardiovascular, gastrointestinal, hepatic, and renal systems [9]. On the other hand, many efforts have been made to prescribe an adequate algorithm for chronic pain treatment. Despite these efforts, the central treatment is focused on opioid pharmacotherapies. Unfortunately, long-term exposure to opioids produces constipation, addictive behavior, tolerance development, and can be a fatal outcome [10]. Moreover, the use of tricyclic antidepressants (TCAs) such as amitriptyline and likewise serotonin and noradrenaline reuptake inhibitors (SNRIs) such as duloxetine and venlafaxine have been associated with somnolence, constipation, dry mouth, and nausea [11]. Furthermore, clinical studies have demonstrated that the prescription of gabapentin or pregabalin is related to somnolence, dizziness, and weight gain; whereas the topical use of lidocaine and capsaicin patches is associated with irritation and local pain [12]. Historically, the wide distribution, use, and acceptance of medicinal plants have been documented in all the regions of Mexico [13][14][15][16][17][18]. In a study carried by Alonso-Castro et al. [13], 28% and 26% of health professionals and physicians, respectively, accepted that they have recommended or prescribed medicinal plants to treat several diseases in their patients. Historically and now, members of the general population have suggested that natural compounds are harmless to the human organism. Because of this, natural products have been used as substitutes for the use of synthetic chemical compounds [19]. However, this is a misconception. It is important to understand that some plants and their derivates might produce side and adverse effects, as well as toxicity and death [20]. In our opinion, the current exploration of the chemical composition, toxicology, dosage, and ethnopharmacology of Mexican herbalism is an urgent area of study for the rational use of traditional medicine. In this respect, there are extensive summaries about the ethnopharmacology of Mexican traditional plants and their derivates, which are popularly employed to treat the most common afflictions. Antibacterial [21] antiparasitic [22], antidiabetic [23] anxiolytic or antidepressant [24][25], anti-cancer [26][27], and cardiovascular [28] effects exhibited by Mexican herbalism products have been demonstrated in preclinical studies. On the other hand, the use of medicinal plants to treat headaches, rheumatic pain, and chronic pain conditions has been documented in Mexican culture [29][30][31]. In this field, there has not been a review of the anti-pain properties of these plants, focusing on the mechanism of actions and adverse effects produced by the most consumed plants in the Mexican population.

2. Future Directions in Preclinical Assays for Mexican Medicinal Plants

We attempt to contextualize the advances in preclinical assays of Mexican traditional plants and their derivates employed in the treatment of inflammatory or neuropathic pain conditions. Approximately thirty-seven plants have been studied regarding their antinociceptives properties (Table 1).

Table 1. Mexican medicinal plants and their antinociceptive effects. This table contains a summary of preclinical studies with medicinal plants, as well as the possible mechanisms of action that underlie their antinociceptive effects.

Plant Type of Extract Experimental Model Species Possible Mechanism of Action Reference
Salvia divinorum Salvinorin A (11.6, 13.9, 18.5, 20.8 and 23.1 nmol, i.t.) Tail flick test Mice Activation of kappa-opioid receptors [32]
Salvia divinorum Salvinorin A (0.5, 1.0, 2.0 and 4.0 mg/kg, i.p.) Tail flick test
Hot plate test
Acetic acid-induced writhing		 Male Swiss mice Activation of kappa-opioid receptors [33]
Salvia divinorum Acetonic extract (30, 100 and 200 mg/kg, i.p.) Sciatic loose nerve ligature-induced mechanical and thermal hyperalgesia
Carrageenan-induced edema		 Male Wistar rats Activation of kappa-opioid receptors [34]
Salvia divinorum Ethyl acetate extract (31.6, 100 and 316 mg/kg, i.p.) and
Mixure salvinorins (30 mg/kg, i.p)		 Acetic acid-induced writhing
Formalin test		 Male and female Swiss albino mice Opioids and 5-HT1A [35]
Heliopsis longipes Ethanolic extract (10, 30, 100 and 300 mg/kg. i.p.) Thermal hyperalgesia Balb/c mice Not studied [36]
Heliopsis longipes Ethanolic extract (10, 30, 100 and 300 mg/kg, p.o.) Carrageenan-induced hyperalgesia (hot box test) Male Balb/c mice Synergistic actions with diclofenac [37]
Heliopsis longipes Ethanolic extract (3, 10, 30 and 100 mg/kg, p.o.) Acetic acid-induced writhing
Hot plate		 Male CD1+ mice Not studied [38]
Heliopsis longipes Affinin (1, 3, 10, 100, 300 and 600 µg/region),
Longipinamide A andLlongipenamide B compounds
(0.1, 1, 10, 30 and 100 µg/region)		 Formalin-induced orofacial pain Female Swiss Webster mice TRPV1 [39]
Heliopsis longipes Ethanolic extract (10 mg/kg, i.p.)
Afinin (1 mg/kg, i.p.)		 Acetic acid-induced writhing
Hot plate test		 Male albino mice Not studied [40]
Heliopsis longipes Acetonic extract (1, 10, 17.78, 31.6, 56.23 mg/kg, i.p.)
Affinin (10, 17.78, 31.62, 56.23, 74.98 mg/kg, i.p.)		 Capsaicin-induced hyperalgesia
Acetic acid-induced writhing		 Male ICR mice Activation of nitric oxide, K+ channels, opioid, GABAergic and serotonergic system [41]
Artemisia ludoviciana Essential oil (1, 10, 31.6, 100 and 316 mg/kg, i.p.) Hot plate test
Formalin-induced hyperalgesia		 Male ICR mice Activation of Opioid system [42]
Caulerpa mexicana Sulphated polysaccharides (5, 10 and 20 mg/kg i.v.) (5, 10 and 20 mg/kg, s.c.) * Acetic acid-induced writhing (no effect)
Formalin-induced hyperalgesia (no effect)
Carrageenan, dextran, histamine and serotonin -induced paw edema*		 Male and female Swiss mice
Male Wistar rats		 Histamine is the main target of paw edema inflammation [43]
Caulerpa mexicana Methanolic extract
Ethyl acetate extract
Hexanic
Chloroform extract (100 mg/kg, p.o.)		 Formalin-induced hyperalgesia
Acetic acid-induced writhing
Hot plate test
Carrageenan-induced peritonitis		 Female Swiss mice Not studied [44]
Agastache mexicana Hexane extract
Ethyl acetate extract methanolic extract (100 mg/kg, i.p.)
Ursolic acid compound (1, 3, 10, 30 and 100 mg/kg, i.p)		 Acid acetic-induced writhing
Formalin-induced hyperalgesia
Intracolonic stimulation with capsaicin		 Male and female Swiss albino mice and Wistar rats Possible participation of cGMP and 5-HT1A receptors. [45]
Agastache mexicana Ursolic compound (1–100 mg/kg)
Acacetin compound (1–100 mg/kg, i.p.) (1–300 mg/kg p.o.)		 Acetic acid-induced writhing Male and female Swiss albino mice Not studied [46]
Agastache mexicana Hexane extract
Ethyl acetate extract
Methanolic extract
(10, 30, 100, 300 and/or 562.3 mg/kg or 1000 mg/kg, i.p)		 Acetic acid-induced writhing
Formalin-induced hyperalgesia
Hot box test
PIFIR model		 Female Swiss albino mice Not studied [30]
Ligusticum porteri Organic extract
Aqueous extract
Essential oil
(31.6, 100 and 316 mg/kg, p.o.)
Z-ligustilide compound
Z-3-butylidenephthalide compound
Diligustilide compound (10, 31.6, 56.2 mg/kg, p.o.)		 Acetic acid- induced writhing
Hot plate test		 Male ICR mice Not studied [47]
Ligusticum porteri Methanolic-chloroform extract (150, 275 and 300 mg/kg, i.p.) Writhing test Male ICR mice Not studied [48]
Clinopodium mexicanum Aqueous extract (1, 5, 10 and 100 mg/kg, i.p.) Hot plate test Male Swiss Webster mice Not studied [49]
Clinopodium mexicanum 2 (S)-neopincirin (1, 10, 20 and 40 mg/kg, i.p.) Hot plate test Male Swiss Webster mice GABAergic system was involved in the anxiolytic effect exerted by 2(S)-neopincirin [50]
Tilia americana var mexicana Aqueous extract
Quercentin
(30 and 100 mg/kg, i.p.)		 Formalin-induced hyperalgesia
PIFIR model		 Male Wistar rats Activation of 5-HT1A receptors [51]
Acourtia thurberi Decoction (31.6, 100, 316.2 µg/paw and 31.6, 100 and 316.2 mg/kg, p.o.)
Perezone (3.2, 10 and 31.6 µg/paw, s.c.)
Mixure of α-pipitzol, β-pipitzul (3.2, 10 and 31.6 µg/paw, s.c.)
8-β-D-glucopyranosyloxy-4-methoxy-5-methyl-coumarin (3.2, 10 and 31.6 µg/paw, s.c.)		 Formalin-induced hyperalgesia in normal and diabetic mice Male ICR mice Not studied [52]
Cyrtopodium macrobulbon Organic extract
Aqueous extract (31.6, 100 and 316 mg/kg, p.o.)		 Hot plate test
Writhing test		 Male ICR mice Not studied [53]
Ternstroemia sylvatica Chloroform and
Ethanolic extract
(250 and 500 mg/kg i.p.)		 Croton oil- and TAP-induced ear edema Carrageenan-induced paw edema
Acid acetic-induced writhing test
Formalin-induced hyperalgesia		 Male ICR mice Not studied [54]
Conyza filaginoides Organic extract (31, 100 and 316 mg/kg, p.o.)
(1, 10, 30, 56, 100 µg/paw, s.c.)		 Acetic acid-induced writhing
Hot plate test
Formalin-induced hyperalgesia in normal and diabetic mice		 Male ICR mice GABAergic and opioid pathways [55]
Choisya ternata Essential oil
Ethanolic extract
(10, 30 and 100 mg/kg, p.o.)
Methyl N- methylanthranilate compound
Isopropyl N-methylanthranilatePropyl N-methylanthranilate compound (0.3, 1 and 3 mg/kg, p.o.)		 Acetic acid-induced writhing test
Hot plate test		 Male Swiss mice Not studied [56]
Choisya ternata Isopropyl (ISOAN) compound
Methyl (MAN) compound
Propyl N-methylanthranilate (PAN) compound
(0.3, 1 and 3 mg/kg, p.o.)		 Formalin-induced hyperalgesia
Capsaicin and
Glutamate-induced nociception test
Tail flick test
Hot plate test		 Male and female Swiss mice K+ATP channels (ISOAN)
Adrenergic, nitrergic and serotoninergic pathways (ISOAN and MAN)		 [57]
Choisya ternata Essential oil ternanthranin (3, 10 and 30 mg/kg, p.o.) Formalin-induced hyperalgesia
Carrageenan-induced paw edema		 Male Webster mice Reduction of nitric oxide, TNF-α and IL-1β [58]
Mimosa albida Aqueous extract (2.5, 25 and 50 mg/kg, i.p.) Hot plate test
Acetic acid-induced writhing		 Male ICR mice Not involved opioid receptors [59]
Heterotheca inuloides HI-2 fraction (butanol fraction) from the aqueous extract Acetic acid-induced writhing test
Carrageenan-induced paw edema
Dextran-induced paw edema		 Female Wistar rats and male Swiss CD-1 mice Not studied [60]
Heterothecainuloides 7-hydroxy-3,4-dihydrocadalin compound (10, 100 and 1000 µg/paw, s.c.) Formalin-induced hyperalgesia
Mechanical hyperalgesia (Randall–Selitto)
Carrageenan-induced paw edema		 Female Wistar rats Activation the 5-HT1A, 5-HT1B, 5-HT1D, but not opioid receptors [61]
Heterothecainuloides 7-hydroxy-3,4-dihydrocadalin (0.03, 0.3, 3 and 30 mg/kg, p.o.) Formalin induced hyperalgesia in diabetic neuropathy * Female Wistar rats Activation of serotonin, but not opioid receptors. Antioxidant effect (malondialdehyde) [62]
Calea zacatechichi Dichloromethane extract (200 mg/kg, p.o.) Intracolonic instillation of mustard oil test
Acetic acid-induced writhing		 Male C57BL/6N mice Not studied [63]
Calea zacatechichi Aqueous extract (200 mg/kg, p.o.) Hot plate test
Acetic acid-induced writhing		 Male albino Swiss mice Not studied [64]
Geranium bellum Acetone-aqueous extract
(200, 400 and 800 µg/paw, s.c.)
(75, 150 and 300 mg/kg, p.o.)
Geraniin
Corilagin
Quercetin
Ellagic acid
(5–25 mg/kg, p.o.)
Geraniin
Quercentin
Ellagic acid and
Corilagin derivates from AC-AE Geranium bellum		 Formalin-induced hyperalgesia
Acetic acid-induced
Hot plate test		 Male Wistar rats
Female CD1 albino mice		 Not studied [65]
Sphaeralceaangustifolia Chloroform extract
(400 mg/kg, i.p.)		 Carrageenan-induced paw edema Male Sprague-Dawley rats Not studied [66]
Acacia farnesiana Ethanol extract
(400 mg/kg, i.p.)		 Carrageenan-induced paw edema Male Sprague-Dawley rats Not studied [66]
Rubuscoriifolius Chloroform:methanolic extract (1:1) (400 mg/kg, i.p.) Carrageenan-induced paw edema Male Sprague-Dawley rats Not studied [66]
Oenotherarosea Methanolic extract Carrageenan-induced paw edema Male Sprague-Dawley rats Not studied [66]
Oenothera rosea Ethanolic and
Ethyl acetate extract
(50, 100 and 200 mg/kg, p.o.)		 Acetic acid-induced writhing
Hot plate test		 Female NIH Swiss mice Not studied [67]
Chamaedora
tepejilote		 Aqueous extract Carrageenan-induced paw edema Male Sprague-Dawley rats Not studied [66]
Astianthus viminalis Methanolic extract Carrageenan-induced paw edema Male Sprague-Dawley rats Not studied [66]
Brickellia
veronicaefolia		 Methanolic-chloroform extract (150, 300 and 600 mg/kg, p.o.) Writhing test Male ICR mice Not studied [48]
Brickelliapaniculata Methanolic extract Carrageenan-induced paw edema Male Sprague-Dawley rats Not studied [66]
Justiciaspicigera, Methanolic extract Carrageenan-induced paw edema Male Sprague-Dawley rats Not studied [66]
Justicia spicigera Ethanolic extract (50, 100 and 200 mg/kg, p.o.) Formalin-induced hyperalgesia test
Hot plate test
Tail flick test
Acetic acid-induced writhing t		 Male Balb/C mice Not studied [68]
Lantanahispida Methanolic extract Carrageenan-induced paw edema Male Sprague-Dawley rats Not studied [66]
Pittocaulon
bombycophole
P. velatum
P. praecox
P. hintonii		 Dichloromethane extract (100 mg/kg, i.p.) Carrageenan-induced paw edema (no effect) Male Wistar rats Not studied [69]
Swietenia humilis Aqueous extract (10, 31.6, 56.2, 100 and 177 μ/paw, s.c.)
Mexicanolide compound (0.5, 1, 2, 3 and 3.5 μg/paw, s.c.)		 Formalin-induced hyperalgesia in diabetic mice Male ICR mice GABAA, 5-HT2A/C and opiod receptors, as well as the nitrergic system. [70]
Ageratina pichinchensis 3,5-diprenyl-4-hydroxyacetophenone compound
(10, 32, 56 and 100 mg/kg, p.o.)
(100, 128, 320 and 562 mg/kg, p.o.)		 Carrageenan-induced thermal hyperalgesia
Allodynia induced by spinal nerve ligation (L5/L6)		 Male Wistar rats Not studied [71]
Tithonia tubaeformis Hydromethanolic extract (100 and 200 mg/kg, p.o.) Tail immersion test
Acid acetic-induced writhing
Vincristine-induced neuropathy		 Balb/c mice Not studied [72]

Considering the literature reports, this leads us to the following question: What is the future of medicinal plants from Mexico, in the field of pain managment? To understand the problem with translational pain research in the field of Mexican plants and their derivates it is necessary to understand the multidisciplinary factors that historically have not allowed traditional medicine to cross from preclinical to clinical research [73]. Thus, it is important highlight the fact that most of the studies lack description of the mechanisms of action underlying these plants’ antinociceptive effects, as well as lacking toxicological tests or assays related to these plants’ side effects (Table 1). Relatedly, less than half of the studies attributed the plants’ antinociceptive effects to bio-compounds present in the plant, which suggests that most of the studies of the plants used extracts developed using methanol, ethanol, chloroform or other chemicals. Some of these extracts are not candidates for research addressed toward clinical studies. Several studies were performed with commercial compounds and were not necessarily isolated from the medicinal plant studied. Thus the characterization of the phytochemical composition of these plants is urgent, along with the linking of the plants’ effects to these compounds. The development of a commercial product for human use is based on standardized extracts, but it is important to understand their composition in order to define a marker compound for quality control. On the other hand, preclinical assays of Mexican plants and their antinociceptive properties mostly evaluated these plants using the formalin test, carrageenan-induced paw edema, acid acetic-induced writhing and thermal nociception tests, whereas only six studies focused on neuropathy models (Table 1). We consider that these points must be resolved in order to advance the study of pain treatment using Mexican medicinal plants. Finally, in agreement with other authors, we suggest the adoption of new models to evaluate inflammatory and neuropathic pain conditions, to provide effective and predictive behavioral animal models for future clinical trials [74][75].

This entry is adapted from the peer-reviewed paper 10.3390/plants10050865

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