Harpagophytum procumbens Extract Ameliorates Allodynia and Modulates Oxidative and Antioxidant Stress Pathways in a Rat Model of Spinal Cord Injury

Ungerer, Garrett; Cui, Jiankun; Ndam, Tina; Bekemeier, Mikeala; Song, Hailong; Zhao, Yuanli; Siedhoff, Heather R.; Yang, Bo; Appenteng, Michael K.; Greenlief, C. Michael; Miller, Dennis K.; Sun, Grace Y.; Folk, William R.

doi:10.1007/s12017-019-08585-z

Cited by 20 publications

(8 citation statements)

References 60 publications

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“…Nrf2 binds to the antioxidant response element sequence and thereby upregulates the expression of its target genes. One of these Nrf2 target genes, HO-1, regulates antioxidant defense and oxidant signaling [25]. Taking these findings together, Nrf2 and HO-1 can be considered as major oxidative stress sensors.…”

Section: Gene Expression In the Cerebellar Cortexmentioning

confidence: 99%

Cerebellar Blood Flow and Gene Expression in Crossed Cerebellar Diaschisis after Transient Middle Cerebral Artery Occlusion in Rats

Kidani

Hishikawa

Hiramatsu

et al. 2020

IJMS

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Crossed cerebellar diaschisis (CCD) is a state of hypoperfusion and hypometabolism in the contralesional cerebellar hemisphere caused by a supratentorial lesion, but its pathophysiology is not fully understood. We evaluated chronological changes in cerebellar blood flow (CbBF) and gene expressions in the cerebellum using a rat model of transient middle cerebral artery occlusion (MCAO). CbBF was analyzed at two and seven days after MCAO using single photon emission computed tomography (SPECT). DNA microarray analysis and western blotting of the cerebellar cortex were performed and apoptotic cells in the cerebellar cortex were stained. CbBF in the contralesional hemisphere was significantly decreased and this lateral imbalance recovered over one week. Gene set enrichment analysis revealed that a gene set for “oxidative phosphorylation” was significantly upregulated while fourteen other gene sets including “apoptosis”, “hypoxia” and “reactive oxygen species” showed a tendency toward upregulation in the contralesional cerebellum. MCAO upregulated the expressions of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) in the contralesional cerebellar cortex. The number of apoptotic cells increased in the molecular layer of the contralesional cerebellum. Focal cerebral ischemia in our rat MCAO model caused CCD along with enhanced expression of genes related to oxidative stress and apoptosis.

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Section: Gene Expression In the Cerebellar Cortexmentioning

confidence: 99%

Cerebellar Blood Flow and Gene Expression in Crossed Cerebellar Diaschisis after Transient Middle Cerebral Artery Occlusion in Rats

Kidani

Hishikawa

Hiramatsu

et al. 2020

IJMS

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“…Recently, Ungerer et al (2020) used a model of contusion in rodents, causing a spinal cord injury in order to assess the action of HP on locomotor function, responses to stimuli, and neurochemical changes. Furthermore, they used in vitro tests simultaneously using microglias (BV-2) to confirm the anti-inflammatory and antioxidant effects of the extract.…”

Section: Resultsmentioning

confidence: 99%

Devil's claw: action on the central nervous system

Lima¹,

Ribeiro²,

Carpilovsky³

et al. 2020

DS-CS

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The Harpagophytum procumbens (HP), popularly known as "garra do diabo" is a native plant from Africa that has been used for years by traditional medicine for treating a various number of health conditions, among which the inflammatory disturbances stand out. The potential anti-inflammatory and antioxidant effects of the plant stand out since it has in its chemical matrix several bioactive compounds. However, there's still little research that reports the association of HP on the central nervous system (CNS). The objective of this paper was to perform a review of the literature among the assays already described in the literature, in Portuguese and English, using the HP associated with the prevention and treatments of neurological and/or neuropsychiatry disturbances and conditions. The methodology performed is a review of the literature bringing publishes of papers found in the virtual database PubMed, using the descriptors: Harpagophytum procumbens (HP) and Central Nervous System (CNS). In total, 11 articles reported the effects of HP with performance on the CNS. In conclusion, this study reported, in association with previous ones, that the antioxidant action of the HP may be related to neuroprotective results due to a synergism of phenolic glycosylated derivatives such as verbascoside and/or iridoid glycosides such as harpagoside and flavonoids.

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“…We speculate that the elevated bilirubin may be due to some hemolysis in the samples and also to Heme oxygenase-1 (HO-1) catalyzed breakdown of heme. We have recently observed induction of HO-1 in rats treated with H. procumbens aqueous-ethanolic extracts [31], and others have also inferred H. procumbens affects HO-1 expression [32]. Overall Model Test -X 2 = 9.04, df 3, p = .03 Binary logistic regression to predict hemolysis.…”

Section: Discussionmentioning

confidence: 96%

Toxicology studies of aqueous-alcohol extracts of Harpagophytum procumbens subsp. procumbens (Burch.) DC.Ex Meisn. (Pedaliaceae) in female and male rats

Joshi

Parrish

Grunz-Borgmann

et al. 2020

BMC Complement Med Ther

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Background: A variety of medicinal products prepared from secondary tubers of Harpagophytum procumbens subsp. procumbens (Burch.) DC.ex Meisn. (Devil's Claw) and H. zeyheri are marketed in Africa, Europe, the United States, South America and elsewhere, where they are used for inflammatory and musculoskeletal conditions such as arthritis, lower back pain, rheumatism and neuralgia, etc. While clinical studies conducted over the last twenty years support the general safety of such products, infrequent gastrointestinal disturbances (diarrhea, nausea, vomiting, abdominal pain), headache, vertigo and hypersensitivity (allergic) reactions (rash, hives and face swelling) have been documented. Sex-related differences occur in the health conditions for which Devil's Claw products are used, so it is likely that usage is similarly sex-related and so might be side effects and potential toxicities. However toxicologic studies of Devil's Claw products have been conducted primarily with male animals. To address this deficit, we report toxicological studies in female and male rats of several H. procumbens (HP) aqueous-alcohol extracts chemically analyzed by UPLC-MS. Methods: Female and male Sprague Dawley rats were studied for one and three months in groups differing by consumption of diets without and with HP extracts at a 7-10-fold human equivalent dose (HED). Sera were analyzed for blood chemistry, and heart, liver, lung, kidney, stomach, and small and large intestine tissues were examined for histopathology. Treatment group differences for blood chemistry were analyzed by ANOVA with Dunnett's test and significant group differences for endpoints with marginal distributional properties were verified using the Kruskal-Wallis test. Group differences for histopathology were tested using Chi Square analysis. Results: Significant group by sex-related differences in blood chemistry were detected in both studies. Additionally, several sex-related differences occurred between the studies. However, significant histopathology effects associated with the consumption of the extracts were not detected. Conclusion: Toxicologic analysis of Devil's Claw extracts cause significant sex-related effects in blood chemistry. However, in our judgement, none of the observed effects suggest serious toxicity at these doses and durations. Subsequent toxicologic and clinical studies of H. procumbens and other medicines with similar properties should explore in greater detail the basis and consequences of potential sex-related effects.

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Harpagophytum procumbens Extract Ameliorates Allodynia and Modulates Oxidative and Antioxidant Stress Pathways in a Rat Model of Spinal Cord Injury

Cited by 20 publications

References 60 publications

Cerebellar Blood Flow and Gene Expression in Crossed Cerebellar Diaschisis after Transient Middle Cerebral Artery Occlusion in Rats

Cerebellar Blood Flow and Gene Expression in Crossed Cerebellar Diaschisis after Transient Middle Cerebral Artery Occlusion in Rats

Devil's claw: action on the central nervous system

Toxicology studies of aqueous-alcohol extracts of Harpagophytum procumbens subsp. procumbens (Burch.) DC.Ex Meisn. (Pedaliaceae) in female and male rats

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