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29.10.2024 | Original Paper

Preventive and therapeutic effects of ephedrine alkaloids-free Ephedra Herb extract on paclitaxel-induced neuropathic pain

verfasst von: Xuedan Huang, Sumiko Hyuga, Michiho Ito, Yukihiro Goda, Yoshinori Kobayashi

Erschienen in: Journal of Natural Medicines | Ausgabe 1/2025

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Abstract

Currently, there are no effective prophylactic or therapeutic drugs for the treatment of paclitaxel (PTX)-induced peripheral neuropathic pain (PTX-PNP), highlighting the urgent need for the development of effective prophylactic and therapeutic drugs. In this study, we initially compared the efficacy of Ephedra Herb extract (EHE) with that of ephedrine alkaloids-free Ephedra Herb extract (EFE), which lacked ephedrine alkaloids (EAs)-associated side effects, against the onset of PTX-induced mechanical allodynia, thermal hyperalgesia, and cold allodynia in mice. EHE and EFE demonstrated comparable preventive effects on the PTX-PNP in a dose-dependent manner. These results indicated that the preventive properties of EHE were independent of the EAs. Since elderly people are overwhelmingly more susceptible to developing cancer, we considered that EFE has greater benefits than EHE, so we conducted a study focused on the effects of EFE. EFE showed dose-dependent preventive effects on the onset of PTX-PNP. As a result of detailed investigation, coadministration of PTX and EFE (Co-EFE) was more effective than preadministration of EFE alone (Pre-EFE). And the effects of Co-EFE was same with the effect of preadministration of EFE and then coadministration of PTX and EFE (P&C-EFE). Additionally, Co-EFE after the onset of PTX-PNP improved PTX-induced mechanical allodynia, thermal hyperalgesia, and cold allodynia, confirming the therapeutic efficacy of EFE on PTX-PNP. In contrast, goshajinkigan, a Kampo medicine, and diclofenac, a non-steroidal anti-inflammatory drug, showed minimal therapeutic effects on PTX-PNP. These findings demonstrate the significant potential of EFE as a novel, safe prophylactic and therapeutic agent against PTX-PNP.

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Flatters SJL, Dougherty PM, Colvin LA (2017) Clinical and preclinical perspectives on chemotherapy-induced peripheral neuropathy (CIPN): a narrative review. Br J Anaesth 119:737–749. https://doi.org/10.1093/bja/aex229CrossRefPubMed

Zhu L, Chen L (2019) Progress in research on paclitaxel and tumor immunotherapy. Cell Mol Biol Lett 24:40. https://doi.org/10.1186/s11658-019-0164-yCrossRefPubMedPubMedCentral

Dougherty PM, Cata JP, Cordella JV, Burton A, Weng HR (2004) Taxol-induced sensory disturbance is characterized by preferential impairment of myelinated fiber function in cancer patients. Pain 109:132–142. https://doi.org/10.1016/j.pain.2004.01.021CrossRefPubMed

Vasey PA, Jayson GC, Gordon A, Gabra H, Coleman R, Atkinson R, Parkin D, Paul J, Hay A, Kaye SB, Scottish Gynaecological Cancer Trials Group (2004) Phase III randomized trial of docetaxel-carboplatin versus paclitaxel-carboplatin as first-line chemotherapy for ovarian carcinoma. J Natl Cancer Inst 96:1682–1691. https://doi.org/10.1093/jnci/djh323CrossRefPubMed

Seretny M, Currie GL, Sena ES, Ramnarine S, Grant R, MacLeod MR, Colvin LA, Fallon M (2014) Incidence, prevalence, and predictors of chemotherapy-induced peripheral neuropathy: a systematic review and meta-analysis. Pain 155:2461–2470. https://doi.org/10.1016/j.pain.2014.09.020CrossRefPubMed

Palazzo E, Marabese I, Gargano F, Guida F, Belardo C, Maione S (2021) Methods for evaluating sensory, affective and cognitive disorders in neuropathic rodents. Curr Neuropharmacol 19:736–746. https://doi.org/10.2174/1570159X18666200831153117CrossRefPubMedPubMedCentral

Takanashi K, Shibata K, Mizuno K, Komatsu R, Koizumi S (2021) Goshajinkigan attenuates paclitaxel-induced neuropathic pain via cortical astrocytes. Pharmacol Res Perspect 9:e00850. https://doi.org/10.1002/prp2.850CrossRefPubMedPubMedCentral

Staff NP, Fehrenbacher JC, Caillaud M, Damaj MI, Segal RA, Rieger S (2020) Pathogenesis of paclitaxel-induced peripheral neuropathy: a current review of in vitro and in vivo findings using rodent and human model systems. Exp Neurol 324:113121. https://doi.org/10.1016/j.expneurol.2019.113121CrossRefPubMed

Was H, Borkowska A, Bagues A, Tu L, Liu JYH, Lu Z, Rudd JA, Nurgali K, Abalo R (2022) Mechanisms of chemotherapy-induced neurotoxicity. Front Pharmacol 13:750507. https://doi.org/10.3389/fphar.2022.750507CrossRefPubMedPubMedCentral

10.

Hirayama Y, Yoshida Y, Mori M, Tamura K (2020) Effects of the publication of clinical guidelines for the management of chemotherapy-induced peripheral neuropathy on the administration preferences of oncology specialists: Japanese association of supportive care in cancer. Jpn J Clin Oncol 50:897–902. https://doi.org/10.1093/jjco/hyaa056CrossRefPubMed

11.

Hirayama Y, Sasaki J, Dosaka-Akita H, Ishitani K (2016) Survey of the management of chemotherapy-induced peripheral neuropathy in Japan: Japanese society of medical oncology. ESMO Open 1:e000053. https://doi.org/10.1136/esmoopen-2016-000053CrossRefPubMedPubMedCentral

12.

Bruera E, Paice JA (2015) Cancer pain management: safe and effective use of opioids. Am Soc Clin Oncol Educ Book 35:593–599. https://doi.org/10.14694/EdBook_AM.2015.35.e593CrossRef

13.

Mantani N, Oka H (2017) パクリタキセルによる関節痛に麻黄湯が有効であった1例. Kampo Newest Therapy 26:243–245

14.

Nugent-Head J (2014) The first materia medica: The Shen Nong ben cao jing. J Chin Med: 22–26

15.

Huang X, Hyuga S, Amakura Y, Hyuga M, Uchiyama N, Hakamatsuka T, Goda Y, Odaguchi H, Hanawa T, Kobayashi Y (2023) Overlooked switch from transient sedation to sustained excitement in the biphasic effects of Ephedra Herb extract administered orally to mice. J Ethnopharmacol 301:115827. https://doi.org/10.1016/j.jep.2022.115827CrossRefPubMed

16.

Hikino H, Konno C, Takata H, Tamada M (1980) Antiinflammatory principle of Ephedra Herbs. Chem Pharm Bull (Tokyo) 28:2900–2904. https://doi.org/10.1248/cpb.28.2900CrossRefPubMed

17.

Mantani N, Andoh T, Kawamata H, Terasawa K, Ochiai H (1999) Inhibitory effect of Ephedrae herba, an oriental traditional medicine, on the growth of influenza A/PR/8 virus in MDCK cells. Antiviral Res 44:193–200. https://doi.org/10.1016/s0166-3542(99)00067-4CrossRefPubMed

18.

Hyuga S, Shiraishi M, Hyuga M, Goda Y, Hanawa T (2011) Ephedra herba, a major component of maoto, inhibits the HGF-induced motility of human breast cancer MDA-MB-231 cells through suppression of c-Met tyrosine phosphorylation and c-Met expression. J Trad Med 28:128–138

19.

Nakamori S, Takahashi J, Hyuga S, Yang J, Takemoto H, Maruyama T, Oshima N, Uchiyama N, Amakura Y, Hyuga M, Hakamatsuka T, Goda Y, Odaguchi H, Hanawa T, Kobayashi Y (2019) Analgesic effects of Ephedra Herb extract, ephedrine alkaloids-free Ephedra Herb extract, ephedrine, and pseudoephedrine on formalin-induced pain. Biol Pharm Bull 42:1538–1544. https://doi.org/10.1248/bpb.b19-00260CrossRefPubMed

20.

Hyuga S, Hyuga M, Oshima N, Maruyama T, Kamakura H, Yamashita T, Yoshimura M, Amakura Y, Hakamatsuka T, Odaguchi H, Goda Y, Hanawa T (2016) Ephedrine alkaloids-free Ephedra Herb extract: a safer alternative to ephedra with comparable analgesic, anticancer, and anti-influenza activities. J Nat Med 70:571–583. https://doi.org/10.1007/s11418-016-0979-zCrossRefPubMedPubMedCentral

21.

Masocha W, Parvathy SS (2016) Preventative and therapeutic effects of a GABA transporter 1 inhibitor administered systemically in a mouse model of paclitaxel-induced neuropathic pain. PeerJ 4:e2798. https://doi.org/10.7717/peerj.2798CrossRefPubMedPubMedCentral

22.

Andoh T, Kitamura R, Fushimi H, Komatsu K, Shibahara N, Kuraishi Y (2014) Effects of goshajinkigan, hachimijiogan, and rokumigan on mechanical allodynia induced by paclitaxel in mice. J Tradit Complement Med 4:293–297. https://doi.org/10.4103/2225-4110.128906CrossRefPubMedPubMedCentral

23.

Peyghambari F, Dashti-Rahmatabadi MH, Rozabadi MD, Rozabadi RD, Rozabadi FD, Pangalizadeh M, Dehghanimohammadabadi N (2015) Antinociceptive effect of palm date spathe hydroalcoholic extract on acute and chronic pain in mice as compared with analgesic effect of morphine and diclofenac. Adv Biomed Res 4:244. https://doi.org/10.4103/2277-9175.170239CrossRefPubMedPubMedCentral

24.

Chaplan SR, Bach FW, Pogrel JW, Chung JM, Yaksh TL (1994) Quantitative assessment of tactile allodynia in the rat paw. J Neurosci Methods 53:55–63. https://doi.org/10.1016/0165-0270(94)90144-9CrossRefPubMed

25.

Takemoto H, Ito M, Asada Y, Kobayashi Y (2015) Inhalation administration of the sesquiterpenoid aristolen-1(10)-en-9-ol from Nardostachys chinensis has a sedative effect via the GABAergic system. Planta Med 81:343–347. https://doi.org/10.1055/s-0035-1545725CrossRefPubMed

26.

Takemoto H, Takahashi J, Hyuga S, Odaguchi H, Uchiyama N, Maruyama T, Yamashita T, Hyuga M, Oshima N, Amakura Y, Hakamatsuka T, Goda Y, Hanawa T, Kobayashi Y (2018) Ephedrine alkaloids-free Ephedra Herb extract, EFE, has no adverse effects such as excitation, insomnia, and arrhythmias. Biol Pharm Bull 41:247–253. https://doi.org/10.1248/bpb.b17-00803CrossRefPubMed

27.

Carozzi VA, Canta A, Chiorazzi A (2015) Chemotherapy-induced peripheral neuropathy: What do we know about mechanisms? Neurosci Lett 596:90–107. https://doi.org/10.1016/j.neulet.2014.10.014CrossRefPubMed

28.

Jaggi AS, Singh N (2012) Mechanisms in cancer-chemotherapeutic drugs-induced peripheral neuropathy. Toxicology 291:1–9. https://doi.org/10.1016/j.tox.2011.10.019CrossRefPubMed

29.

Nakagawa T, Kaneko S (2017) Roles of transient receptor potential ankyrin 1 in oxaliplatin-induced peripheral neuropathy. Biol Pharm Bull 40:947–953. https://doi.org/10.1248/bpb.b17-00243CrossRefPubMed

30.

Materazzi S, Fusi C, Benemei S, Pedretti P, Patacchini R, Nilius B, Prenen J, Creminon C, Geppetti P, Nassini R (2012) TRPA1 and TRPV4 mediate paclitaxel-induced peripheral neuropathy in mice via a glutathione-sensitive mechanism. Pflugers Arch 463:561–569. https://doi.org/10.1007/s00424-011-1071-xCrossRefPubMed

31.

Chen Y, Yang C, Wang ZJ (2011) Proteinase-activated receptor 2 sensitizes transient receptor potential vanilloid 1, transient receptor potential vanilloid 4, and transient receptor potential ankyrin 1 in paclitaxel-induced neuropathic pain. Neuroscience 193:440–451. https://doi.org/10.1016/j.neuroscience.2011.06.085CrossRefPubMed

32.

Mizuno K, Kono T, Suzuki Y, Miyagi C, Omiya Y, Miyano K, Kase Y, Uezono Y (2014) Goshajinkigan, a traditional Japanese medicine, prevents oxaliplatin-induced acute peripheral neuropathy by suppressing functional alteration of TRP channels in rat. J Pharmacol Sci 125:91–98. https://doi.org/10.1254/jphs.13244fpCrossRefPubMed

33.

Nakamori S, Takahashi J, Hyuga S, Tanaka-Kagawa T, Jinno H, Hyuga M, Hakamatsuka T, Odaguchi H, Goda Y, Hanawa T, Kobayashi Y (2017) Ephedra Herb extract activates/desensitizes transient receptor potential vanilloid 1 and reduces capsaicin-induced pain. J Nat Med 71:105–113. https://doi.org/10.1007/s11418-016-1034-9CrossRefPubMed

34.

Hyuga S, Nakamori S, Amakura Y, Hyuga M, Uchiyama N, Kobayashi Y, Hakamatsuka T, Goda Y, Odaguchi H, Hanawa T (2022) Chapter 34 Analgesic effects of Ephedra herb and ephedrine alkaloids-free Ephedra herb extract (EFE). In: Rajendram R, Patel VB, Preedy VR, Martin CR (eds) Treatments, mechanisms, and adverse reactions of anesthetics and analgesics. Academic Press, pp 385–400. https://doi.org/10.1016/B978-0-12-820237-1.00034-XCrossRef

35.

Lees JG, Makker PGS, Tonkin RS, Abdulla M, Park SB, Goldstein D, Moalem-Taylor G (2017) Immune-mediated processes implicated in chemotherapy-induced peripheral neuropathy. Eur J Cancer 73:22–29. https://doi.org/10.1016/j.ejca.2016.12.006CrossRefPubMed

36.

Esposito MF, Malayil R, Hanes M, Deer T (2019) Unique characteristics of the dorsal root ganglion as a target for neuromodulation. Pain Med 20(Supplement 1):S23–S30. https://doi.org/10.1093/pm/pnz012CrossRefPubMedPubMedCentral

37.

Lagas JS, van der Kruijssen CMM, van de Wetering K, Beijnen JH, Schinkel AH (2009) Transport of diclofenac by breast cancer resistance protein (ABCG2) and stimulation of multidrug resistance protein 2 (ABCC2)-mediated drug transport by diclofenac and benzbromarone. Drug Metab Dispos 37:129–136. https://doi.org/10.1124/dmd.108.023200CrossRefPubMed

38.

Amanullah A, Upadhyay A, Dhiman R, Singh S, Kumar A, Ahirwar DK, Gutti RK, Mishra A (2022) Development and challenges of diclofenac-based novel therapeutics: targeting cancer and complex diseases. Cancers (Basel) 14:4385. https://doi.org/10.3390/cancers14184385CrossRefPubMed

39.

So K (2020) Roles of TRPA1 in painful dysesthesia. Yakugaku Zasshi 140:1–6CrossRefPubMed

40.

Oshima N, Yamashita T, Hyuga S, Hyuga M, Kamakura H, Yoshimura M, Maruyama T, Hakamatsuka T, Amakura Y, Hanawa T, Goda Y (2016) Efficiently prepared ephedrine alkaloids-free Ephedra Herb extract: a putative marker and antiproliferative effects. J Nat Med 70:554–562CrossRefPubMedPubMedCentral

Titel: Preventive and therapeutic effects of ephedrine alkaloids-free Ephedra Herb extract on paclitaxel-induced neuropathic pain
verfasst von: Xuedan Huang
Sumiko Hyuga
Michiho Ito
Yukihiro Goda
Yoshinori Kobayashi
Publikationsdatum: 29.10.2024
Verlag: Springer Nature Singapore
Erschienen in: Journal of Natural Medicines / Ausgabe 1/2025
Print ISSN: 1340-3443
Elektronische ISSN: 1861-0293
DOI: https://doi.org/10.1007/s11418-024-01853-8

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