Dietary Supplements in Chemotherapy-Induced Peripheral Neuropathy: Comparison
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Please note this is a comparison between Version 2 by Jason Zhu and Version 1 by Katarzyna Szklener.

Chemotherapy-induced peripheral neuropathy (CIPN) is one of the main and most prevalent side effects of chemotherapy, significantly affecting the quality of life of patients and the course of chemotherapeutic treatment. Acetyl-L-carnitine, vitamins (group B and E), extracts of medical plants, including goshajinkigan, curcumin and others, unsaturated fatty acids, as well as the diet composed of so-called “sirtuin-activating foods”, could change the typical way of treatment of CIPN, improve the quality of life of patients and maintain the continuity of chemotherapy. 

  • Acetyl-L-Carnitine
  • Chemotherapy-induced peripheral neuropathy
  • Medicinal Plants
  • Vitamin

1. Acetyl-L-Carnitine

Acetyl-L-carnitine (ALC), an acetyl ester of L-carnitine, present in both central and peripheral nervous systems, plays an important role in the oxidation of free fatty acids as well as in the intermediary metabolism [29,30][1][2]. Dietary supplementation of ALC exerts neuroprotective, neurotrophic, anti-depressive and analgesic effects in some painful neuropathies in animal models [31,32,33][3][4][5]. Furthermore, repeated ALC administration has been proven to promote regeneration of the injured nerves, increasing axon regeneration at the transected sciatic nerve stump, and restoring motor functions [29,34][1][6]. It has been proven to be effective in reducing pain in diabetes-related neuropathies, where it also seems to be capable of improving electromyography (EMG) parameters [33,35,36][5][7][8]. Pain reduction is probably caused by both a neuroprotective and a central anti-nociceptive mechanism of ALC [33][5].
Data regarding the effects of oral administration of ALC in Chemotherapy-induced peripheral neuropathy (CIPN) is inconclusive, with some studies proving its ability to prevent and/or treat CIPN, while others not only prove its ineffectiveness but suggest that it might exacerbate this condition [30,36,37][2][8][9]. In the study conducted by Pisano et al. [38][10], focused on the animal model of cisplatin- and paclitaxel-induced neuropathy, ALC co-treatment significantly reduced the severity of sensory loss and potentiated the levels of nerve growth factor (NGF), a neuroprotective agent, thus resulting in significantly reduced severity of neuropathy [38][10]. Furthermore, Flatters et al. [29][1] have proven ALC to prevent the onset of significant, paclitaxel-related pain up to three weeks after administration of the last dose of ALC [29][1]. Moreover, and possibly most importantly, ALC was proven to have no effects on the antitumour activity of the cytostatic drugs [38,39][10][11].
Observations made by Ghirardi et al. [39][11] were consistent with those mentioned above. They argue that the co-administration of ALC was able to prevent the oxaliplatin-related neurotoxicity, assessed using both behavioural and neurophysiological methods. Moreover, it was capable of reversing some neurological damage in the follow-up period after the end of the oxaliplatin therapy [39][11].
Nevertheless, observations made in the clinical trials were not consistent. While Bianchi et al. [40][12] observed a significant reduction in the symptoms of CIPN, a study performed by Hershman et al. [37][9] noticed in the double-blind trial that ALC supplementation was not only ineffective in the prevention of taxane-induced neuropathy in women undergoing breast cancer therapy, but also at 24 weeks of ALC therapy an exacerbation of CIPN was observed. Interestingly, the reason behind that vastly different result is not clear [37,39][9][11].
Although ALC was somewhat capable of attenuating established mechanical hypersensitivity caused by paclitaxel and cisplatin, its efficacy as a treatment option for CIPN is disputable and inefficient in comparison to its ability to prevent the development of painful neuropathy in the first place. As mentioned previously, no study observed an increase in the incidence rate of the CIPN caused by ALC administration, while this drug might potentially result in the exacerbation of the symptoms of the CIPN [29,39][1][11].

2. Vitamin B Group

All vitamins from the B group, consisting of thiamine (B1), riboflavin (B2), niacin (B3), pantothenic acid (B5), pyridoxine (B6), cobalamin (B12), folate, choline, and biotin function as coenzymes in several intermediary metabolic pathways, including neurotransmitter synthesis and neuronal membrane synthesis [41][13]. Deficiency of vitamins from B group, especially B12, is known to cause neuropathies, usually accompanied by paraesthesia, numbness, and ataxia [42,43,44][14][15][16]. Observations regarding malignancy caused by B12 deficiency are in the line with the previous statement [45][17]. The most important factor differentiating cancer-caused deficiency from the “normal” deficiency, is the time frame. The clinically manifested significant decrease in cobalamin intake might take from 5 to 10 years, whereas the levels of vitamin B12 in some cancer affected patients have been proven to decrease rapidly, especially during chemotherapy, and the clinical manifestations are visible already after a few months [45,46,47,48,49][17][18][19][20][21]. Schloss et al. [41][13] reported that vitamin B complex supplementation was statistically ineffective at preventing CIPN as compared to the placebo, although as indicated by the results of the Patient Neurotoxicity Questionnaire (PNQ), patients taking the vitamin B complex perceived a reduction in sensory peripheral neuropathy [41][13]. Importantly, in cases of CIPN coexisting with vitamin B12 deficiency, patients did benefit from the oral supplementation of this medication [41,48][13][20]. Lastly, Abe et al. [50][22] reported that oral vitamin B12 supplementation did not help in the prevention of the CIPN onset. Their study did not include the control group and they compared the efficacy of B12 supplementation versus goshajinkigan—observed incidence of neuropathy was 88.9% and 39.3%, respectively [50][22].

3. Vitamin E

Vitamin E is often regarded as a treatment option for several neuropathies, such as diabetic neuropathy [52,53,54][23][24][25]. Furthermore, it is considered a useful agent for alleviating the symptoms of other chemotherapy-related toxicities [55][26]. Vitamin E is proven to be a strong antioxidant capable of protecting the integrity of cellular membranes from oxidative stress; hence, it might be potentially capable to prevent the free radicals caused nerve damage [54,56,57,58][25][27][28][29]. Furthermore, although infrequent in clinical practice, vitamin E deficiency can be caused by an array of possible conditions including various cancers, such as acute lymphoblastic leukaemia, as well as treatment with chemotherapeutics, and cisplatin in particular [59,60,61,62,63,64][30][31][32][33][34][35]. Importantly, some chemotherapeutics, such as cisplatin and oxaliplatin, exhibit oxidative traits. In the case of oxaliplatin, this ability is proven to be linked to the pathogenesis of CIPN [65,66,67][36][37][38]. Should the observations be applied to CIPN caused by other types of chemotherapy, vitamin E could constitute a potentially excellent treatment option in this type of peripheral neuropathy.
Although the majority of data regarding the feasibility of using vitamin E as a treatment option is consistent, some significant discrepancies can be observed. Pace et al. (2003) [68][39] in a study focused on patients diagnosed with a variety of cancers and treated with cisplatin, discovered a positive impact of vitamin E on the incidence and severity of CIPN. Here, the incidence of neurotoxicity was significantly lower in the group simultaneously treated with vitamin E (30.7%) than it was in the group receiving placebo (85.7%). Furthermore, when measured with a comprehensive neurotoxicity score based on clinical and neurophysiological parameters (a modified neurological symptom score, grading the severity of neuropathy as 1 = mild, 2 = moderate, and more than 2 = severe), the severity of polyneuropathy was also lower in the former group—2 vs. 4.7 respectively [69][40]. This observation was further confirmed by several other studies conducted by: Argyriou (2005) et al. [69][40], Argyriou et al. [70][41], and Argyriou et al. [71][42], who all share the same observations of considerably lower incidence of CIPN in vitamin E receiving group vs. placebo group—25% vs. 73.3% [69][40], 21.4% vs. 68.5% [70][41] and 18.7% vs. 62.5% [71][42] respectively. The same correlation was observed in regard to the severity of CIPN, all three studies measured it with the application of the modified peripheral neuropathy (PNP) score, observing a difference between the vitamin E-receiving group and the placebo group with the results of 3.4 ± 6.3 vs. 11.5 ± 10.6 [69][40], 4.99 ± 1.33 vs. 10.47 ± 10.62 [70][41] and 2.25 ± 5.1 vs. 11 ± 11.63 [71][42] respectively. Pace et al. (2010) [72][43] continued to advocate for the use of vitamin E as a potential medication in CIPN. Their observations were consistent with all the aforementioned studies and confirmed that a group of patients treated with vitamin E exhibited lower incidence (5.9%) of CIPN as compared to a placebo group (41.7%) The severity of neurotoxicity measured with the total neuropathy score (TNS; ranging from 0 to 40, higher values indicate more severe course of neuropathy) also indicated ameliorative capabilities of vitamin E, with a mean TNS of 1.4 vs. 4.1 in vitamin E and placebo groups, respectively [72][43]. Lastly, Agnes et al. [73][44] observed vitamin E to prevent mechanical and cold allodynia caused by oxaliplatin [73][44].
Regardless of all the above-mentioned observations, current data is not entirely conclusive. Studies conducted by Afonseca et al. [74][45] and Salehi et al. [75][46] indicated no positive effects resulting from vitamin E administration as a preventive agent, with this discrepancy potentially resulting from different chemotherapeutics reviewed in other clinical trials or the application of different scales [74,75][45][46]. Furthermore, the study led by Kottshade et al. [76][47] observed that vitamin E administration did not impact the incidence rate of CIPN significantly, although as pointed out by Miao et al. [77][48] in their excellent meta-analysis regarding this topic, the methodology of a Kottschade et al. [76][47] study remains disputable, therefore any conclusions should be made with special care [75,77][46][48]. Another study conducted by Heiba et al. [78][49] further displays the discrepancies between particular studies. Their clinical study indicated that vitamin E supplementation neither decreased the incidence of grade 2 or above neuropathy, nor the neuropathy onset time, yet the duration of the neuropathy was clearly different depending on the placebo group and vitamin E group, 12.5 weeks vs. 5 weeks, respectively [78][49].
It is important to remember that even though vitamin E supplementation can be indicated to be an effective way of preventing CIPN, such treatment is not entirely safe. A prospective, multicentre clinical trial involving 35,533 men observed a 17% increased risk of developing prostate cancer after a long-time vitamin E supplementation, thus, in males, the risks of such therapy might outweigh the potential gain [79][50].

4. Medicinal Plants

Since ancient times, medicinal plants and herbs were used to ameliorate symptoms of a wide variety of different diseases and symptoms, including pain of different kinds, and neurological conditions [80,81,82,83][51][52][53][54]. It is believed that there is a strong rationale for this kind of medication, thus a more detailed review of its medical potential in CIPN treatment can be advised.

4.1. Goshajinkigan

Goshajinkigan (GJG) is a traditional Japanese medicine (Kampo) composed of ten herbs (Rehmanniae, Achyranthis Radix, Corni Fructus, Dioscoreae Rhizoma, Plantaginis Semen, Alismatis Rhizoma, Poria, Moutan Cortex, Cinnamomi Cortex, and Processi Aconiti Radix) mixed in a fixed proportion [84,85,86][55][56][57]. In Japan, GJG is often prescribed as a treatment option used to alleviate the symptoms of diabetic peripheral neuropathy i.e., numbness, cold sensations, and paraesthesia/dysesthesia [87,88,89,90][58][59][60][61].
An animal study conducted by Mizuno et al. [91][62] decided to focus on the TRP channels including Ca2+-permeable nonselective cation channels suggested to serve as thermal, chemical, and mechanical sensors, with a particular focus on TRPA1 and TRPM8 [92,93,94,95,96][63][64][65][66][67]. As observed in the real-time polymerase chain reaction (rtPCR), oxaliplatin increased the expression levels of TRPA1 and TRPM8 mRNA resulting in hypersensitivity to cold, while GJG administration prevented that increase [92][63]. Another animal study was performed by Ushio et al. [97][68], where the reseauthorchers discovered that GJG was capable of preventing oxaliplatin-related cold hyperalgesia, although it had no effect on oxaliplatin-related allodynia. Importantly, the authoresearchers discovered that GJG had no negative effect on oxaliplatin-induced tumour cytotoxicity [97][68].
Nishioka et al. [98][69] sought to investigate the possibility of using GJG as a preventive option for CIPN. A group of patients diagnosed with colorectal cancer treated with a modified FOLFOX6 regime, containing oxaliplatin, was divided into two subgroups, with one subgroup receiving oral administration of GJG every day, and the other receiving placebo. Neuropathy was assessed using the Neurotoxicity Criteria of Debiopharm (DEB-NTC) during every course. Their study claimed that the incidence of grade 3 peripheral neuropathy in the GJG group was significantly lower than in the control group, and after 10 courses of chemotherapy, there were no cases of adverse effects in the study group (0%), while in the placebo-receiving group this number reached 12% (p < 0.01) [98][69]. These observations were further confirmed in the subsequent studies. Kono et al. [87,99][58][70] focused on a similar group of patients diagnosed with colorectal cancer and treated with FOLFOX regime and subdivided similarly to the previous study. Consistently with the research of Nishioka et al., Kono et al. [99][70] found GJG to both decrease the incidence rates of the CIPN, as measured with DEB-NTC, and ameliorate its effects [100][71]. Kono et al. later [87][58] used a different scale, Common Terminology Criteria for Adverse Events (CTC-AE), but the results remained consistent with the previous ones. Here, the incidence rate of grade 2 or greater CIPN, until the 8th cycle of chemotherapy, was 39% in the GJG group and 51% in the placebo group, with the incidence rate of grade 3 CIPN being 7% in the GJG group vs. 13% in the placebo group [87][58]. The last study focused on the FOLFOX6 treated group of patients diagnosed with colorectal cancer was the one performed by Oki et al. [100][71] The patient division introduced in the study, was similar to the division presented in the previous two studies. Importantly, this study contradicted the first two, where authors, using the scale of National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTC) to assess neuropathy, observed that GJG not only did not prevent CIPN, but it might have had a contrary effect. The inciThe incidence of grade 2 or greater neurotoxicity was 50.6% and 31.2% in the GJG and the placebo group respectively [100][71]. The reason for this difference remains unclear, although it might be attributed to the differences in the methodology applied in these studies. Nevertheless, this question remains yet to be answered.
Studies performed by Abe et al. [50][22] and Kawabata et al. [101][72] decided to focus on a different approach, with the main focus being the efficacy of GJG in breast cancer patients suffering from CIPN and treated with docetaxel (in the case of Abe et al.) or paclitaxel (in a case of Kawabata et al.) [50,101][22][72]. Abe et al. [50][22] compared the efficacy of B12 supplementation to GJG supplementation with neuropathy being evaluated according to DEB-NTC, NCI-CTC ver. 3.0, and a visual analogue scale (VAS). The reseauthorchers observed an incidence of neuropathy of 39.3% in the GJG group and 88.9% in the B12 group, with a significantly lower incidence rate of adverse events in the former group [50][22]. Kawabata et al. [101][72] measured the difference in the reduction of CIPN with several questionnaires, as well as CTC-AE v4.0, and their results contradicted some of the previous studies. Here, all patients experienced CIPN of either hands or feet at 4 weeks of study and the entire GJG group experienced CIPN of both hands and feet at 12 weeks, while in the control group only 2 out of 6 patients experienced such condition at this time frame [101][72]. Nevertheless, it is important to mention the differences between the two studies. Abe at al. [50][22] study included no control group, while the group of patients being reviewed in the Kawabata et al. [101][72] study was small, with the GJG group consisting of only 4 patients. Furthermore, both studies used different methods of evaluating the severity of CIPN. The discrepancy in the results between these two studies might be caused by either those factors or a sum of all of them.

4.2. Citrullus colocynthis

Citrullus colocynthis, also known as bitter apple, is a plant used in traditional medicine as an anti-inflammatory, antidiabetic, analgesic, hair growth-promoting, abortifacient, and antiepileptic compound with disputable results [109,110,111,112][73][74][75][76]. In Rostami et al. study focusing on patients diagnosed with CIPN, the effects of treatment with C. colocynthis extract oil were evaluated in the randomized, double-blind, placebo-controlled clinical trial. Unfortunately, C. colocynthis extract oil did not ameliorate the symptoms of CIPN [113][77].

4.3. Matricaria chamomilla

Matricaria chamomilla L. extract contains terpenoids like α-bisabolol and its oxide azulenes, including chamazulene and acetylene derivatives and flavonoids: apigenin, luteolin or others [114][78]. Apigenin was reported to have antioxidative effects, resulting in neuroprotective effects against oxidative stress in neurological disorders [110,115][74][79]. Moreover, apigenin treatment by modulating levels of cytokines and nitric oxide can be protective for neurites and cell viability against inflammation [116,117,118][80][81][82]. In mice models of cisplatin-induced neuropathy, M. chamomilla was able to decrease pain and inflammation which was measured in the formalin test [119][83]. To the best of authors’ knowledge, no clinical trials investigating the feasibility of using M. chamomilla as an ameliorative factor in CIPN have been performed to this day.

4.4. Salvia officinalis

Salvia officinalis, which contains phenolic acid and flavonoid content, has anti-inflammatory and antioxidant effects on lipopolysaccharide-induced inflammation as shown in the mice model. The Salvia officinalis administration resulted in a decrease of inflammatory markers, which, according to the authors’ suggestion, might be caused by the inhibition of reactive lipid peroxidation or/and the consumption of antioxidants by scavenging reactive oxygen radicals [120][84]. This plant can be also useful in the enhancement of cognitive activity and protection against neurodegenerative diseases [121][85]. In Alzheimer’s Disease, S. officinalis improved cognitive functions with no side effects compared to the placebo group [122,123][86][87]. The influence of S. officinalis on CIPN has been shown in a mice model, where its extract increased vincristine-induced pain response [124][88].

4.5. Cinnamomum cassia

Cinnamomum cassia, which contains coumarins, cinnamic acid, as well as cinnamaldehyde, was described as a neuroinflammation-inhibiting compound, capable of exerting its action through attenuation of iNOS, COX-2 expression and NF-κB [125][89]. The study by Kim et al. [126][90] presented that the administration of Cinnamomum Cortex (the bark of C. cassia) water extract could induce a significant suppression of the activation of astrocytes and microglia. After cold allodynia causing oxaliplatin injection, C. Cortex water extract has been observed to decrease the expression levels of IL-1β and TNF in the spinal cord. Moreover, the same study showed that coumarins, the compound of C. Cortex, can attenuate oxaliplatin-induced cold allodynia in rats [126][90].

4.6. Curcumin

Curcumin is a commonly known substance, which positively impacts health by decreasing the risk for several pathologies: cardiovascular diseases [127][91], type 2 diabetes mellitus [128][92], cancer [129][93], but also against neurodegenerative disorders like Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis among others [130][94]. Recent studies have shown that curcumin, with its poor water solubility, cannot act directly on the central nervous system, rather affecting the “microbiota-gut-brain axis”, so that the functions of the brain are preserved [131][95]. Curcumin, due to its influence on NF-ĸB [132][96], COX-2 and pro-inflammatory cytokines [133][97], is also described as an anti-inflammatory, antioxidant, and neuroprotective substance [134][98]. Curcumin, in the mice model, decreases vincristine-induced neuropathic pain including hyperalgesia and allodynia. Additionally, an antioxidative effect has been observed in the curcumin-treated group [135][99]. Agthong et al. [136][100] noticed that curcumin prevented thermal hyperalgesia in rats with cisplatin-induced neuropathy. Moreover, in this study morphometric analysis of L4 dorsal root ganglia was performed, and in the curcumin-treated group less pathological changes, such as nuclear or nucleolar atrophies including the loss of neurons, have been observed [137]. As mentioned previously, one of the pathomechanisms of cisplatin-related neuropathy is oxidative stress caused by this chemotherapeutic.

References

  1. Flatters, S.J.L.; Xiao, W.-H.; Bennett, G.J. Acetyl-l-Carnitine Prevents and Reduces Paclitaxel-Induced Painful Peripheral Neuropathy. Neurosci. Lett. 2006, 397, 219–223.
  2. de Grandis, D. Acetyl-L-Carnitine for the Treatment of Chemotherapy-Induced Peripheral Neuropathy. CNS Drugs 2007, 21, 39–43.
  3. Sima, A.A.; Ristic, H.; Merry, A.; Kamijo, M.; Lattimer, S.A.; Stevens, M.J.; Greene, D.A. Primary Preventive and Secondary Interventionary Effects of Acetyl-L-Carnitine on Diabetic Neuropathy in the Bio-Breeding Worcester Rat. J. Clin. Investig. 1996, 97, 1900–1907.
  4. Lowitt, S.; Malone, J.I.; Salem, A.F.; Korthals, J.; Benford, S. Acetyl-l-Carnitine Corrects the Altered Peripheral Nerve Function of Experimental Diabetes. Metabolism 1995, 44, 677–680.
  5. di Stefano, G.; di Lionardo, A.; Galosi, E.; Truini, A.; Cruccu, G. Acetyl-L-Carnitine in Painful Peripheral Neuropathy: A Systematic Review. J. Pain Res. 2019, 12, 1341–1351.
  6. Fernandez, E.; Pallini, R.; Gangitano, C.; del Fá, A.; Sangiacomo, C.O.; Sbriccoli, A.; Ramon Ricoy, J.; Rossi, G.F. Effects of L-Carnitine, L-Acetylcarnitine and Gangliosides on the Regeneration of the Transected Sciatic Nerve in Rats. Neurol. Res. 1989, 11, 57–62.
  7. Veronese, N.; Sergi, G.; Stubbs, B.; Bourdel-Marchasson, I.; Tessier, D.; Sieber, C.; Strandberg, T.; Gillain, S.; Barbagallo, M.; Crepaldi, G.; et al. Effect of Acetyl-l-Carnitine in the Treatment of Diabetic Peripheral Neuropathy: A Systematic Review and Meta-Analysis. Eur. Geriatr. Med. 2017, 8, 117–122.
  8. de Grandis, D.; Minardi, C. Acetyl-L-Carnitine (Levacecarnine) in the Treatment of Diabetic Neuropathy. Drugs R D 2002, 3, 223–231.
  9. Hershman, D.L.; Unger, J.M.; Crew, K.D.; Minasian, L.M.; Awad, D.; Moinpour, C.M.; Hansen, L.; Lew, D.L.; Greenlee, H.; Fehrenbacher, L.; et al. Randomized Double-Blind Placebo-Controlled Trial of Acetyl-L-Carnitine for the Prevention of Taxane-Induced Neuropathy in Women Undergoing Adjuvant Breast Cancer Therapy. J. Clin. Oncol. 2013, 31, 2627–2633.
  10. Pisano, C.; Pratesi, G.; Laccabue, D.; Zunino, F.; lo Giudice, P.; Bellucci, A.; Pacifici, L.; Camerini, B.; Vesci, L.; Castorina, M.; et al. Paclitaxel and Cisplatin-Induced Neurotoxicity: A Protective Role of Acetyl-L-Carnitine. Clin. Cancer Res. Off. J. Am. Assoc. Cancer Res. 2003, 9, 5756–5767.
  11. Ghirardi, O.; lo Giudice, P.; Pisano, C.; Vertechy, M.; Bellucci, A.; Vesci, L.; Cundari, S.; Miloso, M.; Rigamonti, L.M.; Nicolini, G.; et al. Acetyl-L-Carnitine Prevents and Reverts Experimental Chronic Neurotoxicity Induced by Oxaliplatin, without Altering Its Antitumor Properties. Anticancer Res. 2005, 25, 2681–2687.
  12. Bianchi, G.; Vitali, G.; Caraceni, A.; Ravaglia, S.; Capri, G.; Cundari, S.; Zanna, C.; Gianni, L. Symptomatic and Neurophysiological Responses of Paclitaxel- or Cisplatin-Induced Neuropathy to Oral Acetyl-l-Carnitine. Eur. J. Cancer 2005, 41, 1746–1750.
  13. Schloss, J.M.; Colosimo, M.; Airey, C.; Masci, P.; Linnane, A.W.; Vitetta, L. A Randomised, Placebo-Controlled Trial Assessing the Efficacy of an Oral B Group Vitamin in Preventing the Development of Chemotherapy-Induced Peripheral Neuropathy (CIPN). Support. Care Cancer 2017, 25, 195–204.
  14. Lindenbaum, J.; Healton, E.B.; Savage, D.G.; Brust, J.C.M.; Garrett, T.J.; Podell, E.R.; Margell, P.D.; Stabler, S.P.; Allen, R.H. Neuropsychiatric Disorders Caused by Cobalamin Deficiency in the Absence of Anemia or Macrocytosis. N. Engl. J. Med. 1988, 318, 1720–1728.
  15. Healton, E.B.; Savage, D.G.; Brust, J.C.M.; Garrett, T.J.; Lindenbaum, J. Neurologic Aspects of Cobalamin Deficiency. Medicine 1991, 70, 229–245.
  16. Wolffenbuttel, B.H.R.; Wouters, H.J.C.M.; Heiner-Fokkema, M.R.; van der Klauw, M.M. The Many Faces of Cobalamin (Vitamin B12) Deficiency. Mayo Clin. Proc. Innov. Qual. Outcomes 2019, 3, 200–214.
  17. Solomon, L.R. Functional Vitamin B12 Deficiency in Advanced Malignancy: Implications for the Management of Neuropathy and Neuropathic Pain. Support. Care Cancer 2016, 24, 3489–3494.
  18. Schloss, J.; Colosimo, M. B Vitamin Complex and Chemotherapy-Induced Peripheral Neuropathy. Curr. Oncol. Rep. 2017, 19, 76.
  19. Shipton, M.J.; Thachil, J. Vitamin B12 Deficiency—A 21st Century Perspective. Clin. Med. 2015, 15, 145.
  20. Schloss, J.M.; Colosimo, M.; Airey, C.; Vitetta, L. Chemotherapy-Induced Peripheral Neuropathy (CIPN) and Vitamin B12 Deficiency. Support. Care Cancer 2015, 23, 1843–1850.
  21. Vu, T.; Amin, J.; Ramos, M.; Flener, V.; Vanyo, L.; Tisman, G. New Assay for the Rapid Determination of Plasma Holotranscobalamin II Levels: Preliminary Evaluation in Cancer Patients. Am. J. Hematol. 1993, 42, 202–211.
  22. Abe, H.; Kawai, Y.; Mori, T.; Tomida, K.; Kubota, Y.; Umeda, T.; Tani, T. The Kampo Medicine Goshajinkigan Prevents Neuropathy in Breast Cancer Patients Treated with Docetaxel. Asian Pac. J. Cancer Prev. 2013, 14, 6351–6356.
  23. Granados-Principal, S.; Quiles, J.L.; Ramirez-Tortosa, C.L.; Sanchez-Rovira, P.; Ramirez-Tortosa, M. New Advances in Molecular Mechanisms and the Prevention of Adriamycin Toxicity by Antioxidant Nutrients. Food Chem. Toxicol. 2010, 48, 1425–1438.
  24. Tütüncü, N.B.; Bayraktar, M.; Varli, K. Reversal of Defective Nerve Conduction with Vitamin E Supplementation in Type 2 Diabetes: A Preliminary Study. Diabetes Care 1998, 21, 1915–1918.
  25. Ng, Y.T.; Phang, S.C.W.; Tan, G.C.J.; Ng, E.Y.; Botross Henien, N.P.; Palanisamy, U.D.M.; Ahmad, B.; Abdul Kadir, K. The Effects of Tocotrienol-Rich Vitamin E (Tocovid) on Diabetic Neuropathy: A Phase II Randomized Controlled Trial. Nutrients 2020, 12, 1522.
  26. Kalkanis, J.G.; Whitworth, C.; Rybak, L.P. Vitamin E Reduces Cisplatin Ototoxicity. Laryngoscope 2004, 114, 538–542.
  27. Kamoona, T.H.; Hameed, H.Y.; Mohammad, A.R.; Farhan, A.H. Docetaxel Chemotherapy Induced Peripheral Neuropathy in Breast Cancer Patients and Its Amelioration by Vitamin E. Kufa Med. J. 2017, 17, 13–27.
  28. Shamsaei, G.; Ahmadzadeh, A.; Mehraban, N. The Vitamin E Preventive Effect on Taxol-Induced Neuropathy among Patients with Breast Cancer: A Randomized Clinical Trial. Jundishapur J. Nat. Pharm. Prod. 2017; in press.
  29. Lee, P.; Ulatowski, L.M. Vitamin E: Mechanism of Transport and Regulation in the CNS. IUBMB Life 2019, 71, 424–429.
  30. Bove, L.; Picardo, M.; Maresca, V.; Jandolo, B.; Pace, A. A Pilot Study on the Relation between Cisplatin Neuropathy and Vitamin E. J. Exp. Clin. Cancer Res. CR 2001, 20, 277–280.
  31. Kennedy, D.D.; Tucker, K.L.; Ladas, E.D.; Rheingold, S.R.; Blumberg, J.; Kelly, K.M. Low Antioxidant Vitamin Intakes Are Associated with Increases in Adverse Effects of Chemotherapy in Children with Acute Lymphoblastic Leukemia. Am. J. Clin. Nutr. 2004, 79, 1029–1036.
  32. Dasgupta, J.; Sanyal, U.; Das, S. Vitamin E—Its Status and Role in Leukemia and Lymphoma. Neoplasma 1993, 40, 235–240.
  33. Battisti, V.; Maders, L.D.K.; Bagatini, M.D.; Santos, K.F.; Spanevello, R.M.; Maldonado, P.A.; Brulé, A.O.; do Araújo, M.C.; Schetinger, M.R.C.; Morsch, V.M. Measurement of Oxidative Stress and Antioxidant Status in Acute Lymphoblastic Leukemia Patients. Clin. Biochem. 2008, 41, 511–518.
  34. Weijl, N.I.; Hopman, G.D.; Wipkink-Bakker, A.; Lentjes, E.G.W.M.; Berger, H.M.; Cleton, F.J.; Osanto, S. Cisplatin Combination Chemotherapy Induces a Fall in Plasma Antioxidants of Cancer Patients. Ann. Oncol. 1998, 9, 1331–1337.
  35. Kava, M.; Walsh, P.; SrinivasJois, R.; Cole, C.; Lewis, B.; Nagarajan, L. Clinical and Electrophysiological Characteristics of Vincristine Induced Peripheral Neuropathy in Children. J. Int. Child Neurol. Assoc. 2017, 1.
  36. Cepeda, V.; Fuertes, M.A.; Castilla, J.; Alonso, C.; Quevedo, C.; Perez, J.M. Biochemical Mechanisms of Cisplatin Cytotoxicity. Anti-Cancer Agents Med. Chem. 2007, 7, 3–18.
  37. Taşlı, N.G.; Uçak, T.; Karakurt, Y.; Keskin Çimen, F.; Özbek Bilgin, A.; Kurt, N.; Süleyman, H. The Effects of Rutin on Cisplatin Induced Oxidative Retinal and Optic Nerve Injury: An Experimental Study. Cutan. Ocul. Toxicol. 2018, 37, 252–257.
  38. Yu, W.; Chen, Y.; Dubrulle, J.; Stossi, F.; Putluri, V.; Sreekumar, A.; Putluri, N.; Baluya, D.; Lai, S.Y.; Sandulache, V.C. Cisplatin Generates Oxidative Stress Which Is Accompanied by Rapid Shifts in Central Carbon Metabolism. Sci. Rep. 2018, 8, 4306.
  39. Pace, A.; Savarese, A.; Picardo, M.; Maresca, V.; Pacetti, U.; del Monte, G.; Biroccio, A.; Leonetti, C.; Jandolo, B.; Cognetti, F.; et al. Neuroprotective Effect of Vitamin E Supplementation in Patients Treated with Cisplatin Chemotherapy. J. Clin. Oncol. 2003, 21, 927–931.
  40. Argyriou, A.A.; Chroni, E.; Koutras, A.; Ellul, J.; Papapetropoulos, S.; Katsoulas, G.; Iconomou, G.; Kalofonos, H.P. Vitamin E for Prophylaxis against Chemotherapy-Induced Neuropathy: A Randomized Controlled Trial. Neurology 2005, 64, 26–31.
  41. Argyriou, A.A.; Chroni, E.; Koutras, A.; Iconomou, G.; Papapetropoulos, S.; Polychronopoulos, P.; Kalofonos, H.P. A Randomized Controlled Trial Evaluating the Efficacy and Safety of Vitamin E Supplementation for Protection against Cisplatin-Induced Peripheral Neuropathy: Final Results. Support. Care Cancer 2006, 14, 1134–1140.
  42. Argyriou, A.A.; Chroni, E.; Koutras, A.; Iconomou, G.; Papapetropoulos, S.; Polychronopoulos, P.; Kalofonos, H.P. Preventing Paclitaxel-Induced Peripheral Neuropathy: A Phase II Trial of Vitamin E Supplementation. J. Pain Symptom Manag. 2006, 32, 237–244.
  43. Pace, A.; Giannarelli, D.; Galie, E.; Savarese, A.; Carpano, S.; della Giulia, M.; Pozzi, A.; Silvani, A.; Gaviani, P.; Scaioli, V.; et al. Vitamin E Neuroprotection for Cisplatin Neuropathy: A Randomized, Placebo-Controlled Trial. Neurology 2010, 74, 762–766.
  44. Agnes, J.P.; dos Santos, V.W.; das Neves, R.N.; Gonçalves, R.M.; Delgobo, M.; Girardi, C.S.; Lückemeyer, D.D.; de Ferreira, M.A.; Macedo-Júnior, S.J.; Lopes, S.C.; et al. Antioxidants Improve Oxaliplatin-Induced Peripheral Neuropathy in Tumor-Bearing Mice Model: Role of Spinal Cord Oxidative Stress and Inflammation. J. Pain 2021, 22, 996–1013.
  45. Afonseca, S.O.; de Cruz, F.M.; de Cubero, D.I.G.; Lera, A.T.; Schindler, F.; Okawara, M.; de Souza, L.F.; Rodrigues, N.P.; del Giglio, A. Vitamin E for Prevention of Oxaliplatin-Induced Peripheral Neuropathy: A Pilot Randomized Clinical Trial. Sao Paulo Med. J. 2013, 131, 35–38.
  46. Salehi, Z.; Roayaei, M. Effect of Vitamin E on Oxaliplatin-Induced Peripheral Neuropathy Prevention: A Randomized Controlled Trial. Int. J. Prev. Med. 2015, 6, 104.
  47. Kottschade, L.A.; Sloan, J.A.; Mazurczak, M.A.; Johnson, D.B.; Murphy, B.P.; Rowland, K.M.; Smith, D.A.; Berg, A.R.; Stella, P.J.; Loprinzi, C.L. The Use of Vitamin E for the Prevention of Chemotherapy-Induced Peripheral Neuropathy: Results of a Randomized Phase III Clinical Trial. Support. Care Cancer 2011, 19, 1769–1777.
  48. Miao, H.; Li, R.; Chen, D.; Hu, J.; Chen, Y.; Xu, C.; Wen, Z. Protective Effects of Vitamin E on Chemotherapy-Induced Peripheral Neuropathy: A Meta-Analysis of Randomized Controlled Trials. Ann. Nutr. Metab. 2021, 77, 127–137.
  49. Heiba, M.A.; Ismail, S.S.; Sabry, M.; Bayoumy, W.A.E.; Kamal, K.A.-A. The Use of Vitamin E in Preventing Taxane-Induced Peripheral Neuropathy. Cancer Chemother. Pharmacol. 2021, 88, 931–939.
  50. Klein, E.A.; Thompson, I.M.; Tangen, C.M.; Crowley, J.J.; Lucia, M.S.; Goodman, P.J.; Minasian, L.M.; Ford, L.G.; Parnes, H.L.; Gaziano, J.M.; et al. Vitamin E and the Risk of Prostate Cancer. JAMA 2011, 306, 1549.
  51. Luo, Y.; Wang, C.-Z.; Sawadogo, R.; Tan, T.; Yuan, C.-S. Effects of Herbal Medicines on Pain Management. Am. J. Chin. Med. 2020, 48, 1–16.
  52. Makkar, R.; Behl, T.; Bungau, S.; Zengin, G.; Mehta, V.; Kumar, A.; Uddin, M.S.; Ashraf, G.M.; Abdel-Daim, M.M.; Arora, S.; et al. Nutraceuticals in Neurological Disorders. Int. J. Mol. Sci. 2020, 21, 4424.
  53. Lee, B.; Kwon, C.-Y.; Chang, G.T. Oriental Herbal Medicine for Neurological Disorders in Children: An Overview of Systematic Reviews. Am. J. Chin. Med. 2018, 46, 1701–1726.
  54. Oveissi, V.; Ram, M.; Bahramsoltani, R.; Ebrahimi, F.; Rahimi, R.; Naseri, R.; Belwal, T.; Devkota, H.P.; Abbasabadi, Z.; Farzaei, M.H. Medicinal Plants and Their Isolated Phytochemicals for the Management of Chemotherapy-Induced Neuropathy: Therapeutic Targets and Clinical Perspective. DARU J. Pharm. Sci. 2019, 27, 389–406.
  55. Toume, K.; Hou, Z.; Yu, H.; Kato, M.; Maesaka, M.; Bai, Y.; Hanazawa, S.; Ge, Y.; Andoh, T.; Komatsu, K. Search of Anti-Allodynic Compounds from Plantaginis Semen, a Crude Drug Ingredient of Kampo Formula “Goshajinkigan”. J. Nat. Med. 2019, 73, 761–768.
  56. Cascella, M.; Muzio, M.R. Potential Application of the Kampo Medicine Goshajinkigan for Prevention of Chemotherapy-Induced Peripheral Neuropathy. J. Integr. Med. 2017, 15, 77–87.
  57. Kaku, H.; Kumagai, S.; Onoue, H.; Takada, A.; Shoji, T.; Miura, F.; Yoshizaki, A.; Sato, S.; Kigawa, J.; Arai, T.; et al. Objective Evaluation of the Alleviating Effects of Goshajinkigan on Peripheral Neuropathy Induced by Paclitaxel/Carboplatin Therapy: A Multicenter Collaborative Study. Exp. Ther. Med. 2012, 3, 60–65.
  58. Kono, T.; Hata, T.; Morita, S.; Munemoto, Y.; Matsui, T.; Kojima, H.; Takemoto, H.; Fukunaga, M.; Nagata, N.; Shimada, M.; et al. Goshajinkigan Oxaliplatin Neurotoxicity Evaluation (GONE): A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial of Goshajinkigan to Prevent Oxaliplatin-Induced Neuropathy. Cancer Chemother. Pharmacol. 2013, 72, 1283–1290.
  59. Watanabe, K.; Shimada, A.; Miyaki, K.; Hirakata, A.; Matsuoka, K.; Omae, K.; Takei, I. Long-Term Effects of Goshajinkigan in Prevention of Diabetic Complications: A Randomized Open-Labeled Clinical Trial. Evid. Based Complement. Altern. Med. 2014, 2014, 128726.
  60. Tawata, M.; Kurihara, A.; Nitta, K.; Iwase, E.; Gan, N.; Onaya, T. The Effects of Goshajinkigan, a Herbal Medicine, on Subjective Symptoms and Vibratory Threshold in Patients with Diabetic Neuropathy. Diabetes Res. Clin. Pract. 1994, 26, 121–128.
  61. Nishizawa, M.; Sutherland, W.H.F.; Nukada, H. Gosha-Jinki-Gan (Herbal Medicine) in Streptozocin-Induced Diabetic Neuropathy. J. Neurol. Sci. 1995, 132, 177–181.
  62. Mizuno, K.; Kono, T.; Suzuki, Y.; Miyagi, C.; Omiya, Y.; Miyano, K.; Kase, Y.; Uezono, Y. Goshajinkigan, a Traditional Japanese Medicine, Prevents Oxaliplatin-Induced Acute Peripheral Neuropathy by Suppressing Functional Alteration of TRP Channels in Rat. J. Pharmacol. Sci. 2014, 125, 91–98.
  63. Wang, H.; Woolf, C.J. Pain TRPs. Neuron 2005, 46, 9–12.
  64. McKemy, D.D.; Neuhausser, W.M.; Julius, D. Identification of a Cold Receptor Reveals a General Role for TRP Channels in Thermosensation. Nature 2002, 416, 52–58.
  65. Colburn, R.W.; Lubin, M.L.; Stone, D.J.; Wang, Y.; Lawrence, D.; D’Andrea, M.R.; Brandt, M.R.; Liu, Y.; Flores, C.M.; Qin, N. Attenuated Cold Sensitivity in TRPM8 Null Mice. Neuron 2007, 54, 379–386.
  66. Story, G.M.; Peier, A.M.; Reeve, A.J.; Eid, S.R.; Mosbacher, J.; Hricik, T.R.; Earley, T.J.; Hergarden, A.C.; Andersson, D.A.; Hwang, S.W.; et al. ANKTM1, a TRP-like Channel Expressed in Nociceptive Neurons, Is Activated by Cold Temperatures. Cell 2003, 112, 819–829.
  67. Bandell, M.; Story, G.M.; Hwang, S.W.; Viswanath, V.; Eid, S.R.; Petrus, M.J.; Earley, T.J.; Patapoutian, A. Noxious Cold Ion Channel TRPA1 Is Activated by Pungent Compounds and Bradykinin. Neuron 2004, 41, 849–857.
  68. Ushio, S.; Egashira, N.; Sada, H.; Kawashiri, T.; Shirahama, M.; Masuguchi, K.; Oishi, R. Goshajinkigan Reduces Oxaliplatin-Induced Peripheral Neuropathy without Affecting Anti-Tumour Efficacy in Rodents. Eur. J. Cancer 2012, 48, 1407–1413.
  69. Nishioka, M.; Shimada, M.; Kurita, N.; Iwata, T.; Morimoto, S.; Yoshikawa, K.; Higashijima, J.; Miyatani, T.; Kono, T. The Kampo Medicine, Goshajinkigan, Prevents Neuropathy in Patients Treated by FOLFOX Regimen. Int. J. Clin. Oncol. 2011, 16, 322–327.
  70. Kono, T.; Mamiya, N.; Chisato, N.; Ebisawa, Y.; Yamazaki, H.; Watari, J.; Yamamoto, Y.; Suzuki, S.; Asama, T.; Kamiya, K. Efficacy of Goshajinkigan for Peripheral Neurotoxicity of Oxaliplatin in Patients with Advanced or Recurrent Colorectal Cancer. Evid. Based Complement. Altern. Med. 2011, 2011, 418481.
  71. Oki, E.; Emi, Y.; Kojima, H.; Higashijima, J.; Kato, T.; Miyake, Y.; Kon, M.; Ogata, Y.; Takahashi, K.; Ishida, H.; et al. Preventive Effect of Goshajinkigan on Peripheral Neurotoxicity of FOLFOX Therapy (GENIUS Trial): A Placebo-Controlled, Double-Blind, Randomized Phase III Study. Int. J. Clin. Oncol. 2015, 20, 767–775.
  72. Kawabata, K.; Kawajiri, H.; Takashima, T.; Nakano, T.; Mitukawa, Y.; Kawakami, N. Reduction of Paclitaxel-Related Peripheral Sensory Neuropathy by Gosha-Jinki-Gan or Carbon Dioxide Feet and Hand Bathing. Ann. Oncol. 2013, 24, ix80.
  73. Cornblath, D.R.; Chaudhry, V.; Carter, K.; Lee, D.; Seysedadr, M.; Miernicki, M.; Joh, T. Total Neuropathy Score. Neurology 1999, 53, 1660.
  74. Riaz, H.; Chatha, S.A.S.; Hussain, A.I.; Bukhari, S.A.; Hussain, S.M.; Zafar, K. Physico-Chemical Characterization of Bitter Apple (Citrullus Colosynthis) Seed Oil and Seed Residue. Int. J. Biosci. 2015, 6, 283–292.
  75. Hussain, A.I.; Rathore, H.A.; Sattar, M.Z.A.; Chatha, S.A.S.; Sarker, S.D.; Gilani, A.H. Citrullus Colocynthis (L.) Schrad (Bitter Apple Fruit): A Review of Its Phytochemistry, Pharmacology, Traditional Uses and Nutritional Potential. J. Ethnopharmacol. 2014, 155, 54–66.
  76. Rahimi, R.; Amin, G.; Ardekani, M.R.S. A Review on Citrullus Colocynthis Schrad: From Traditional Iranian Medicine to Modern Phytotherapy. J. Altern. Complement. Med. 2012, 18, 551–554.
  77. Rostami, N.; Mosavat, S.H.; Heydarirad, G.; Arbab Tafti, R.; Heydari, M. Efficacy of Topical Citrullus Colocynthis (Bitter Apple) Extract Oil in Chemotherapy-induced Peripheral Neuropathy: A Pilot Double-blind Randomized Placebo-controlled Clinical Trial. Phytother. Res. 2019, 33, 2685–2691.
  78. Srivastava, J.K.; Shankar, E.; Gupta, S. Chamomile: A Herbal Medicine of the Past with a Bright Future (Review). Mol. Med. Rep. 2010, 3, 895–901.
  79. Kim, M.; Jung, J.; Jeong, N.Y.; Chung, H.-J. The Natural Plant Flavonoid Apigenin Is a Strong Antioxidant That Effectively Delays Peripheral Neurodegenerative Processes. Anat. Sci. Int. 2019, 94, 285–294.
  80. Nabavi, S.F.; Khan, H.; D’onofrio, G.; Šamec, D.; Shirooie, S.; Dehpour, A.R.; Argüelles, S.; Habtemariam, S.; Sobarzo-Sanchez, E. Apigenin as Neuroprotective Agent: Of Mice and Men. Pharmacol. Res. 2018, 128, 359–365.
  81. Guzik, T.J.; Korbut, R.; Adamek-Guzik, T. Nitric Oxide and Superoxide in Inflammation and Immune Regulation. J. Physiol. Pharmacol. Off. J. Pol. Physiol. Soc. 2003, 54, 469–487.
  82. Goodman, R.B.; Pugin, J.; Lee, J.S.; Matthay, M.A. Cytokine-Mediated Inflammation in Acute Lung Injury. Cytokine Growth Factor Rev. 2003, 14, 523–535.
  83. Abad, A.N.A.; Nouri, M.H.K.; Gharjanie, A.; Tavakoli, F. Effect of Matricaria Chamomilla Hydroalcoholic Extract on Cisplatin-Induced Neuropathy in Mice. Chin. J. Nat. Med. 2011, 9, 126–131.
  84. Kolac, U.K.; Ustuner, M.C.; Tekin, N.; Ustuner, D.; Colak, E.; Entok, E. The Anti-Inflammatory and Antioxidant Effects of Salvia Officinalis on Lipopolysaccharide-Induced Inflammation in Rats. J. Med. Food 2017, 20, 1193–1200.
  85. Lopresti, A.L. Salvia (Sage): A Review of Its Potential Cognitive-Enhancing and Protective Effects. Drugs R D 2017, 17, 53–64.
  86. Akhondzadeh, S.; Noroozian, M.; Mohammadi, M.; Ohadinia, S.; Jamshidi, A.H.; Khani, M. Salvia Officinalis Extract in the Treatment of Patients with Mild to Moderate Alzheimer’s Disease: A Double Blind, Randomized and Placebo-Controlled Trial. J. Clin. Pharm. Ther. 2003, 28, 53–59.
  87. Miroddi, M.; Navarra, M.; Quattropani, M.C.; Calapai, F.; Gangemi, S.; Calapai, G. Systematic Review of Clinical Trials Assessing Pharmacological Properties of Salvia Species on Memory, Cognitive Impairment and Alzheimer’s Disease. CNS Neurosci. Ther. 2014, 20, 485–495.
  88. Abad, A.N.A.; Nouri, M.H.K.; Tavakkoli, F. Effect of Salvia Officinalis Hydroalcoholic Extract on Vincristine-Induced Neuropathy in Mice. Chin. J. Nat. Med. 2011, 9, 354–358.
  89. Chen, Y.-F.; Wang, Y.-W.; Huang, W.-S.; Lee, M.-M.; Wood, W.G.; Leung, Y.-M.; Tsai, H.-Y. Trans-Cinnamaldehyde, An Essential Oil in Cinnamon Powder, Ameliorates Cerebral Ischemia-Induced Brain Injury via Inhibition of Neuroinflammation Through Attenuation of INOS, COX-2 Expression and NFκ-B Signaling Pathway. NeuroMol. Med. 2016, 18, 322–333.
  90. Kim, C.; Lee, J.H.; Kim, W.; Li, D.; Kim, Y.; Lee, K.; Kim, S.K. The Suppressive Effects of Cinnamomi Cortex and Its Phytocompound Coumarin on Oxaliplatin-Induced Neuropathic Cold Allodynia in Rats. Molecules 2016, 21, 1253.
  91. Li, H.; Sureda, A.; Devkota, H.P.; Pittalà, V.; Barreca, D.; Silva, A.S.; Tewari, D.; Xu, S.; Nabavi, S.M. Curcumin, the Golden Spice in Treating Cardiovascular Diseases. Biotechnol. Adv. 2020, 38, 107343.
  92. Pivari, F.; Mingione, A.; Brasacchio, C.; Soldati, L. Curcumin and Type 2 Diabetes Mellitus: Prevention and Treatment. Nutrients 2019, 11, 1837.
  93. Giordano, A.; Tommonaro, G. Curcumin and Cancer. Nutrients 2019, 11, 2376.
  94. Bhat, A.; Mahalakshmi, A.M.; Ray, B.; Tuladhar, S.; Hediyal, T.A.; Manthiannem, E.; Padamati, J.; Chandra, R.; Chidambaram, S.B.; Sakharkar, M.K. Benefits of Curcumin in Brain Disorders. BioFactors 2019, 45, 666–689.
  95. di Meo, F.; Margarucci, S.; Galderisi, U.; Crispi, S.; Peluso, G. Curcumin, Gut Microbiota, and Neuroprotection. Nutrients 2019, 11, 2426.
  96. Chauhan, P.S.; Singh, D.K.; Dash, D.; Singh, R. Intranasal Curcumin Regulates Chronic Asthma in Mice by Modulating NF-ĸB Activation and MAPK Signaling. Phytomedicine 2018, 51, 29–38.
  97. Menon, V.P.; Sudheer, A.R. Antioxidant and Anti-Inflammatory Properties of Curcumin. In The Molecular Targets and Therapeutic Uses of Curcumin in Health and Disease; Springer: Boston, MA, USA, 2007; pp. 105–125.
  98. Cole, G.M.; Teter, B.; Frautschy, S.A. Neuroprotective Effects of Curcumin. In The Molecular Targets and Therapeutic Uses of Curcumin in Health and Disease; Springer: Boston, MA, USA, 2007; pp. 197–212.
  99. Babu, A.; Prasanth, K.G.; Balaji, B. Effect of Curcumin in Mice Model of Vincristine-Induced Neuropathy. Pharm. Biol. 2015, 53, 838–848.
  100. Agthong, S.; Kaewsema, A.; Charoensub, T. Curcumin Ameliorates Functional and Structural Abnormalities in Cisplatin-Induced Neuropathy. Exp. Neurobiol. 2015, 24, 139–145.
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