<i>Justicia flava</i> Leaves Exert Mild Estrogenic Activity in Mouse Models of Uterotrophic and Reproductive Cycle Investigations

Bafor, Enitome E.; Ukpebor, Faith; Elvis-Offiah, Uloma B.; Uchendu, Adaeze P; Omoruyi, Osemelomen; Omogiade, Glory U.

doi:10.1089/jmf.2019.0155

Cited by 10 publications

(9 citation statements)

References 34 publications

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“…It is worth mentioning that there is currently relevant interest among research groups in evaluating a possible analgesic, anti-inflammatory and antiulcerogenic activity. A diversity of special metabolites is found in Justicia , mainly alkaloids [ 46 , 47 , 48 , 49 , 50 , 51 ], steroids [ 52 , 53 , 54 ], tannins [ 32 , 41 , 46 , 51 ], terpenoids [ 47 , 48 , 51 , 54 , 55 , 56 , 57 , 58 ], lignans [ 59 , 60 , 61 , 62 , 63 , 64 ] and flavonoids [ 16 , 20 , 21 , 22 , 23 , 24 , 31 , 32 , 51 , 65 , 66 , 67 ].…”

Section: Introductionmentioning

confidence: 99%

Overview of the Justicia Genus: Insights into Its Chemical Diversity and Biological Potential

et al. 2023

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The genus Justicia has more than 600 species distributed in both hemispheres, in the tropics and temperate regions, and it is used in the treatment of numerous pathologies. This study presents a review of the biological activities of plant extracts and isolated chemical constituents of Justicia (ACANTHACEAE), identified in the period from May 2011 to August 2022. We analyzed over 176 articles with various biological activities and chemical compound descriptions present in the 29 species of Justicia. These have a variety of applications, such as antioxidant and antimicrobial, with alkaloids and flavonoids (e.g., naringenin) the most frequently identified secondary metabolites. The most observed species were Justicia gendarussa Burm., Justicia procumbens L., Justicia adhatoda L., Justicia spicigera Schltdl, and Justicia pectoralis Jacq. The frontier molecular orbitals carried out using density functional theory (M062X and basis set 6-311++G(d,p) indicate reactive sites for naringenin compound and a chemical reaction on phytomedicine activity. The energy gap (206.99 kcal/mol) and dimer solid state packing point to chemical stability. Due to the wide variety of pharmacological uses of these species, this review points toward the development of new phytomedicines.

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Section: Introductionmentioning

confidence: 99%

Overview of the Justicia Genus: Insights into Its Chemical Diversity and Biological Potential

et al. 2023

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“…Estrous phase lasts between 12 -48 hours (approximately 2 day) and signifies the beginning of the luteal period in humans [18,19]. Estrus is the stage when the female mice remain sexually receptive ("on heat" or "in heat").…”

Section: Estrus Phasementioning

confidence: 99%

Our Clear-Cut Improvement to the Impact of Mouse and Rat Models in the Research Involving Female Reproduction

Elvis-Offiah¹,

Isuman²,

Johnson³

et al. 2023

Animal Models and Experimental Research in Medicine

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In most research involving female reproductive function, female animals particularly mice and rats are usually employed. This may perhaps be due to their well-defined reproductive cycle (estrous cycle) as well as the ability to breed and handle them easily. The short and precise length of estrus cycle usually 4–5 days make mice models the choicest mammal when it comes to human related research. Also, they possess very short reproductive age typically 7–8 months reaching sexual maturity at weeks 4–7 following their birth. Although many similarities exist between this model and humans, however, there also exist obvious distinctions between the human female reproductive system and that of mice. Humans have average length of their reproductive or menstrual cycle of about 28–29 days with their reproductive ages between 10–40 years. These relevant differences between mice and human reproductive system constitute the limitations to the use of this models. Therefore, the scope of this chapter will be to explore the basic knowledge of laboratory mice by examining their reproductive system anatomy and physiology, the fertilization process, estrous cycle and genetic make-up. We hope that this will provide many insights to the use of animal models in female reproductive research.

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“…Moreover, a recent review on natural products for tocolysis found that most plant extracts for inhibition of uterine contractions belong to flavonoid or terpene classes [16]. Interestingly, plant extracts containing flavonoids have shown tocolytic effects (J. flava, B. pinnatum, T. paniculatum), with B. pinnatum entering into a clinical trial that was, unfortunately, withdrawn early due to lack of patient enrollment [17][18][19][20][21][22]. Therefore, mundulone and MA belong to an interesting class of compounds to study for tocolytic potential.…”

Section: Introductionmentioning

confidence: 99%

Identification of mundulone and mundulone acetate as natural products with tocolytic efficacy in mono- and combination-therapy with current tocolytics

Siricilla

et al. 2021

Preprint

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Currently, there are a lack of FDA-approved tocolytics for the management of preterm labor. We previously observed that the isoflavones mundulone and mundulone acetate (MA) inhibit intracellular Ca2+-regulated myometrial contractility. Here, we further probed the potential of these natural products to be small molecule leads for discovery of novel tocolytics by: (1) examining uterine-selectivity by comparing concentration-response between human primary myometrial cells and a major off-target site, aortic vascular smooth muscle cells (VSMCs), (2) identifying synergistic combinations with current clinical tocolytics to increase efficacy or and reduce off-target side effects, (3) determining cytotoxic effects and (4) investigating the efficacy, potency and tissue-selectivity between myometrial contractility and constriction of fetal ductus arteriosus (DA), a major off-target of current tocolytics. Mundulone displayed significantly greater efficacy (Emax = 80.5% vs. 44.5%, p=0.0005) and potency (IC50 = 27 μM and 14 μM, p=0.007) compared to MA in the inhibition of intracellular-Ca2+ from myometrial cells. MA showed greater uterine-selectivity, compared to mundulone, based on greater differences in the IC50 (4.3 vs. 2.3 fold) and Emax (70% vs. 0%) between myometrial cells compared to aorta VSMCs. Moreover, MA demonstrated a favorable in vitro therapeutic index of 8.8, compared to TI = 0.8 of mundulone, due to its significantly (p<0.0005) smaller effect on the viability of myometrial (hTERT-HM), liver (HepG2) and kidney (RPTEC) cells. However, mundulone exhibited synergism with two current tocolytics (atosiban and nifedipine), while MA only displayed synergistic efficacy with only nifedipine. Of these synergistic combinations, only mundulone + atosiban demonstrated a favorable TI = 10 compared to TI=0.8 for mundulone alone. While only mundulone showed concentration-dependent inhibition of ex vivo mouse myometrial contractions, neither mundulone or MA affected mouse fetal DA vasoreactivity. The combination of mundulone and atosiban yielded greater tocolytic efficacy and potency on term pregnant mouse and human myometrial tissue compared to single-drugs. Collectively, these data highlight the difference in uterine‐selectivity of Ca2+‐mobilization, effects on cell viability and tocolytic efficacy between mundulone and MA. These natural products could benefit from medicinal chemistry efforts to study the structural activity relationship for further development into a promising single- and/or combination-tocolytic therapy for management of preterm labor.

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Justicia flava Leaves Exert Mild Estrogenic Activity in Mouse Models of Uterotrophic and Reproductive Cycle Investigations

Cited by 10 publications

References 34 publications

Overview of the Justicia Genus: Insights into Its Chemical Diversity and Biological Potential

Overview of the Justicia Genus: Insights into Its Chemical Diversity and Biological Potential

Our Clear-Cut Improvement to the Impact of Mouse and Rat Models in the Research Involving Female Reproduction

Identification of mundulone and mundulone acetate as natural products with tocolytic efficacy in mono- and combination-therapy with current tocolytics

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