Myrciaria dubia Juice (camu-camu) Exhibits Analgesic and Antiedematogenic Activities in Mice

다국어 초록 (Multilingual Abstract)

The Myrciaria dubia (Myrtaceae) fruit is traditionally used to treat malnutrition due to its high levels of vitamin C and phenolic compounds. Because of its composition, this plant is very promising in the research of novel natural treatment for pain disorders. This study analyzed the phytochemical profile of M. dubia juice and assessed its antinociceptive and antiedematogenic potential. The phytochemical profile was determined through high-performance liquid chromatography (HPLC), the oral antinociceptive effect of M. dubia 50% juice (Md50) was evaluated by formalin, hot plate and Complete Freund's Adjuvant tests and the antiedematogenic activity by paw edema. HPLC revealed the presence of ascorbic acid, rutin, and ellagic acid as major compounds. Md50 showed an antinociceptive effect in the acute and chronic phases of the formalin test. In the hot plate test, Md50 also induced an antinociceptive effect of 0.5 up to 6 h, showing antinociceptive and antiedematogenic potential without changing the spontaneous locomotion of animals. All protocols were submitted and approved by the Ethics Committee for use of Animals of the Lutheran University of Brazil (protocol No. 2013-30P).

참고문헌 (Reference)

1 Inoue T, "Tropical fruit camucamu(Myrciaria dubia)has anti-oxidative and anti-inflammatory properties" 52 : 127-132, 2008

2 Zuccotto F, "Through the ‘‘Gatekeeper Door’’ : Exploiting the active kinase conformation" 53 : 2681-2694, 2010

3 Chung JM, "The role of reactive oxygen species(ROS)in persistent pain" 4 : 248-250, 2004

4 Chang HP, "The protective role of carotenoids and polyphenols in patients with head and neck caˆncer" 78 : 89-95, 2015

5 Hunskaar S, "The formalin test in mice : Dissociation between inflammatory and non-inflammatory pain" 30 : 103-114, 1987

6 Dubuisson D, "The formalin test : A quantitative study of the analgesic effects of morphine, meperidine, and brain stem stimulation in rats and cats" 4 : 61-174, 1977

7 Aydin D, "The effect of combined treatment of alpha-tocopherol, ascorbic acid, and pyridoxine with NMDA blocker memantine on penicillin-induced epileptiform activity in rats" 43 : 245-250, 2013

8 Nemirovsky A, "The antinociceptive effect of the combination of spinal morphine with systemic morphine or uprenorphine" 93 : 197-203, 2001

9 Tjo¨lsen A, "The Pharmacology of pain (Handbook of Experimental Pharmacology series. v. 25)" Springer Verlag 1-20, 1997

10 Yuyama LKO, "Teores de elementos minerais em algumas populac¸o˜es de camu-camu" 4 : 549-555, 2003

11 Franke SIR, "Study of antioxidant and mutagenic activity of different orange juices" 88 : 45-55, 2004

12 Petho˜ G, "Sensory and signaling mechanisms of bradykinin, eicosanoids, platelet-activating factor, and nitric oxide in peripheral nociceptors" 92 : 1699-1775, 2012

13 Oliveira RS, "Quimiopreventive action of phytochemicals through regulation of transcription factor Nrf2 : Integrative literature review" 66 : e07428-, 2020

14 Chaplan SR, "Quantitative assessment of tactile allodynia in the rat paw" 53 : 55-63, 1994

15 Reynertson KA, "Quantitative analysis of antiradical phenolic constituents from fourteen edible Myrtaceae fruits" 109 : 883-890, 2011

16 Sharath Badu GR, "Pelargonidin modulates Keap1/Nrf2 pathway gene expression and ameliorates citrinin-induced oxidative stress in HepG2 cells" 8 : 868-, 2017

17 Rocha APC, "Pain : Current aspects on peripheral and central sensitization" 57 : 94-105, 2007

18 Alwarith J, "Nutrition interventions in rheumatoid arthritis : The potential use of plant-based diets. A Review" 6 : 141-, 2019

19 Ankier SI, "New hot plate tests to quantify antinociceptive and narcotic antagonist activities" 27 : 1-4, 1976

20 Sucupira NR, "Methods for measuring antioxidant activity of fruits. UNOPAR Cient" 14 : 263-269, 2012

21 Gainok J, "Investigation of the anti-inflammatory, antinociceptive effect of ellagic acid as measured by digital paw pressure via the Randall-Selitto meter in male Sprague–Dawley rats" 79 : 28-34, 2011

22 Divi RL, "Inhibition of thyroid peroxidase by dietary flavonoids" 9 : 16-23, 1996

23 Raso GM, "Inhibition of inducible nitric oxide synthase and cyclooxigenase-2-expression by flavonoids in macrophage J774A" 68 : 921-931, 2001

24 Cuman RKN, "Influence of type 2 diabetes on the inflammatory response in rat" 50 : 460-465, 2001

25 Oliveira Ju´nior JO, "Inflammatory mediators os neurophatic pain" 17 : 35-42, 2016

26 Gupta SC, "Inflammation, a double-edge sword for cancer and other agerelated diseases" 9 : 2160-, 2018

27 Hossain H, "HPLC profiling, antioxidant and in vivo antiinflammatory activity of the ethanol extract of Syzygium jambos available in Bangladesh" 9 : 191-, 2016

28 Andre´ E, "Evidence for the involvement of vanilloid receptor in the antinociception produced by the dialdeı´ydes unsaturated sesquiterpenes polygodial and drimanial in rats" 46 : 590-597, 2004

29 Rosa KA, "Evidence for the involvement of glutamatergic system in the antinociceptive effect of ascorbic acid" 381 : 185-188, 2005

30 Fracassetti D, "Ellagic acid derivatives, ellagitannins, proanthocyanidins and other phenolics, vitamin C and antioxidant capacity of two powder products from camu-camu fruit(Myrciaria dubia)" 15 : 578-588, 2013

31 Dixon WJ, "Efficient analysis of experimental observations" 20 : 441-462, 1980

32 Calder PC, "Dietary factors and low-grade inflammation in relation to overweight and obesity" 10 : S5-S78, 2011

33 Zanatta CF, "Determination of anthocyanins from camu-camu(Myrciaria dubia)by HPLC-PDA, HPLC-MS, and NMR" 53 : 9531-9535, 2005

34 Soares JC, "Comprehensive characterization of bioactive phenols from new Brazilian superfruits by LC-ESI-QTOF-MS, and their ROS and RNS scavenging effects and anti-inflammatory activity" 281 : 178-188, 2019

35 Appel K, "Chokeberry(Aronia melanocarpa(Michx. )Elliot concentrate inhibits NF-jB and synergizes with selenium to inhibit the release of pro-inflammatory mediators in macrophages" 105 : 73-82, 2015

36 Courvoisier H, "Behavioral and neuroendocrine reactivity to stress in the WKHA/WKY inbred rat strains : A multifactorial and genetic analysis" 743 : 77-85, 1996

37 Afsar T, "Antipyretic, antiinflammatory and analgesic activity of Acacia hydaspica R. Parker and its phytochemical analysis" 15 : 136-, 2015

38 Brozo´ska MM, "Antioxidants as a potential preventive and therapeutic strategy for cadmium" 16 : 1-, 2015

39 Hernandez-Ortega M, "Antioxidant, antinociceptive, and anti-inflammatory effects of carotenoids extracted from dried pepper(Capsicum annum L. )" 12 : 1-10, 2012

40 Filipsky´ T, "Antioxidant effects of coumarins include direct radical scavenging, metal chelation and inhibition of ROSproducing enzymes" 15 : 415-431, 2015

41 Basting RT, "Antinociceptive, anti-inflammatory and gastroprotective effects of a hydroalcoholic extract from the leaves of Eugenia punicifolia(Kunth)DC. in rodents" 157 : 257-267, 2014

42 Oliveira SM, "Antinociceptive effect of 3-(4-fluorophenyl)-5-trifluoromethyl-1H-1-tosylpyrazole. A Celecoxib structural analog in models of pathological pain" 124 : 396-404, 2014

43 Da Silva FC, "Antigenotoxic effect of acute, subacute and chronic treatments with Amazonian camucamu(Myrciaria dubia)juice on mice blood cells" 50 : 2275-2281, 2012

44 Da Silva FC, "Antigenotoxic and antimutagenic effects of Myrciaria dubia juice in mice submitted to ethanol 28-day treatment" 82 : 956-968, 2019

45 Lopes AJO, "AntiInflammatory and antinociceptive activity of pollen extract collected by stingless bee Melipona fasciculata" 20 : 4512-, 2019

46 Kang HS, "Anti-inflammatory activity of arctigenin from Forsythiae Fructus" 116 : 305-312, 2008

47 Afridi R, "Anti-hyperalgesic properties of a flavanone derivative Poncirin in acute and chronic inflammatory pain models in mice" 20 : 57-, 2019

48 Ashmawi HA, "Analgesic effect of histamine H1 receptor antagonists in a model of formalininduced pain in rats" 59 : 461-470, 2009

49 Souza AH, "An evaluation of the antinociceptive effects of Phalpha1beta, a neurotoxin from the spider Phoneutria nigriventer, and omega-conotoxin MVIIA, a cone snail Conus magus toxin, in rat model of inflammatory and neuropathic pain" 33 : 59-67, 2013

50 Ueda H, "Aldose reductase inhibitors from the leaves of Myrciaria dubia(H. B. & K. )McVaugh" 11 : 652-656, 2004

51 Sweitzer SM, "Acute peripheral inflammation induces moderate glial activation and spinal IL-1b expression that correlates with pain behavior in the rat" 829 : 209-221, 1999

52 Matto V, "Acute and chronic citalopram treatment differently modulates rat exploratory behavior in the exploration box test : No evidence for increased anxiety or changes in the [3H] raclopride binding" 58 : 59-69, 1999

53 Akachi T, "1-Methylmalate from camu-camu(Myrciaria dubia)suppressed d-galactosamine-induced liver injury in rats" 74 : 573-578, 2010