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Scopoletin-standardized Morinda elliptica leaf extract suppressed inflammation and cartilage degradation to alleviate osteoarthritis: A preclinical study

Wan Osman WN, Lau SF, Mohamed S

Phytother Res, 2017 Dec;31(12):1954-1961.
PMID: 29067744 DOI: 10.1002/ptr.5949

The effect of scopoletin-standardized Morinda elliptica leaf extract against osteoarthritis was investigated in ex vivo explant culture and preclinical rodent model. Thirty male rats were grouped (n = 6) into untreated osteoarthritis (OA), OA + Diclofenac (5 mg/kg), and OA + extract (200 and 400 mg/kg) and compared with healthy control. Monosodium iodoacetate were injected into the right intra-articular knee joints to induce OA. The rats were evaluated for OA severity via physical (micro-CT and histological observations), biochemical, ELISA, and mRNA expression analysis (for inflammation and cartilage degradation biomarkers), after 28 days of treatment. The extract suppressed glycosaminoglycan release from the cartilage explant in the presence of Interleukin-1β. The 200 mg/kg dose appeared better than 400 mg/kg dose, at reducing cartilage and subchondral bone erosions in OA-induced rats, by significantly down-regulating the collagenases and aggrecanase. The extract dose-dependently reduced serum inflammation biomarkers and increased bone formation biomarkers to near normal levels in the OA-induced rats. M. elliptica leaf scopoletin-standardised extract alleviated OA progression and articular cartilage structure, by ameliorating cartilage degradation, nitric oxide levels, inflammation, bone /cartilage homeostasis, collagenase/aggrecanase activities, chondrocytes survival, subchondral bone structure and integrity.

Matched MeSH terms: Morinda/chemistry*
Noni (Morinda citrifolia Linn.) fruit juice attenuates the rewarding effect of ethanol in conditioned place preference in mice

Pandy V, Khan Y

Exp Anim, 2016 Nov 1;65(4):437-445.
PMID: 27333840

Morinda citrifolia L. commonly known as noni or Indian mulberry belongs to the family Rubiaceae. Noni fruit juice has recently become a very popular remedy for the treatment of several diseases, including psychiatric disorders. This study aimed to investigate the anticraving effect of Tahitian Noni® Juice (TNJ) against ethanol seeking behavior in ICR male mice using the conditioned place preference (CPP) test. The CPP procedure consisted of four phases: preconditioning, conditioning, extinction, and reinstatement. During conditioning, intraperitoneal (i.p.) injections of ethanol (2 g/kg body weight (bw)) and normal saline (10 ml/kg bw) were given on alternate days for 12 days. Then, the animals were subjected to extinction trials for the next 12 days to weaken CPP. Finally, CPP was reinstated in the extinguished animals by a single low-dose priming injection of ethanol (0.4 g/kg bw, i.p.). The effect of TNJ (as a source of drinking water) on different phases of ethanol CPP in mice was studied. TNJ-treated mice showed a significant reduction in ethanol seeking behavior in the CPP test. The reference drug, acamprosate (ACAM) also showed a similar effect in the CPP test. The outcome of this study suggests that TNJ is effective in attenuating ethanol craving in mice and could be utilized for the treatment of alcohol dependence. Further clinical studies in this direction are warranted to support the present preclinical findings.

Matched MeSH terms: Morinda
Fulltext Characterization and purification of protease extracted from two maturity stages of ‘noni’ (Morinda citrifolia L.) fruit

Normah Ismail, Nurulain Abd Razak

Scientific Research Journal, 2014;11(2):0-0.
MyJurnal

Protease was extracted from two maturity stages of noni fruits (Morinda citrifolia L.), unripe (stage 1) and ripe (stage 5). The crude extract was partially purified by acetone precipitation method followed by dialysis, gel filtration chromatography and freeze drying. Protein concentrations, proteolytic activity, molecular weight distribution, pH stability, temperature stability and storage efficiency of the resulting protease were evaluated. The unripe and ripe noni fruit contains 0.65 and 0.35% protein, respectively. Molecular weight of the proteases from both stages ranged approximately between 3 to 28 kDa based on the SDS-PAGE results. The optimum activity were at pH 7s and 6, temperatures of 40 and 50°C, respectively for proteases obtained from the unripe and ripe fruit. Analysis from the freeze dried protease indicated that protease from ripe noni fruits had higher protein concentration and specific activity compared to those from unripe fruit. However, it is more sensitive to pH and temperature and less stable during storage as it shows lower proteolytic activity compared to protease from unripe fruit. Based on its high proteolytic activity reaching up to 70.31 U/mg and storage stability (30% lost of activity), noni fruit could be an alternative source of plant protease.

Matched MeSH terms: Morinda
Methanolic Extract of Morinda citrifolia L. (Noni) Unripe Fruit Attenuates Ethanol-Induced Conditioned Place Preferences in Mice

Khan Y, Pandy V

Front Pharmacol, 2016;7:352.
PMID: 27729866

Phytotherapy is an emerging field successfully utilized to treat various chronic diseases including alcohol dependence. In the present study, we examined the effect of the standardized methanolic extract of Morinda citrifolia Linn. unripe fruit (MMC), on compulsive ethanol-seeking behavior using the mouse conditioned place preference (CPP) test. CPP was established by injections of ethanol (2 g/kg, i.p.) in a 12-day conditioning schedule in mice. The effect of MMC and the reference drug, acamprosate (ACAM), on the reinforcing properties of ethanol in mice was studied by the oral administration of MMC (1, 3, and 5 g/kg) and ACAM (300 mg/kg) 60 min prior to the final CPP test postconditioning. Furthermore, CPPs weakened with repeated testing in the absence of ethanol over the next 12 days (extinction), during which the treatment groups received MMC (1, 3, and 5 g/kg, p.o.) or ACAM (300 mg/kg, p.o.). Finally, a priming injection of a low dose of ethanol (0.4 g/kg, i.p.) in the home cage (Reinstatement) was sufficient to reinstate CPPs, an effect that was challenged by the administration of MMC or ACAM. MMC (3 and 5 g/kg, p.o.) and ACAM (300 mg/kg, p.o.) significantly reversed the establishment of ethanol-induced CPPs and effectively facilitated the extinction of ethanol CPP. In light of these findings, it has been suggested that M. citrifolia unripe fruit could be utilized for novel drug development to combat alcohol dependence.

Matched MeSH terms: Morinda
Kesan Pemberian Ekstrak Buah Mengkudu (Morinda citrifolia Linn.) ke atas Kualiti Sperma dan Histologi Testis Mencit (Effect of Mengkudu (Morinda citrifolia Linn.) Extract on Sperm Quality and Histology of Testis in Mice)

Mahanem Mat Noor, Chuay SH

Sains Malaysiana, 2004;33.

The mengkudu (Morinda citrifolia Linn.) plant is a well known medicinal plant. The fruits, leaves and roots of this plant have been widely used in traditional medicine. The purpose of this study was to evaluate the effects of an aqueous extract of the M. citrifolia fruits (25 mg/kg, 50 mg/kg and 100 mg/kg body weight given for a period of 30 days) on sperm quality and histology of testis in mice. Data from this study show that the epididymal sperm count, mortality, motility and sperm morphology in mice given the M. citrifolia fruit extract did not differ from that of the control group. Spermatogenesis was not affected by the treatment. The results obtained here suggest that the aqueous extract of the M. citrifolia fruit (up to 100 mg/kg) did not affect sperm quality and spermatogenesis in mice.
Mengkudu (Morinda citrifolia Linn.) adalah tumbuhan ubatan yang terkenal. Bahagian buah, daun dan akarnya digunakan secara meluas dalam perubatan tradisional. Kajian ini dijalankan untuk menentukan kesan pemberian ekstrak berakua buah M. citrifolia (dos 25mg/kg, 50 mg/kg dan 100 mg/kg berat tubuh mencit selama 30 hari) ke atas kuantiti sperma dan histologi testis mencit. Data daripada kajian ini menunjukkan bilangan sperma epididimis, mortaliti, motiliti dan morfologi sperma mencit kajian tidak berbeza berbanding kumpulan kawalan. Proses spermatogenesis juga tidak terjejas dengan pemberian M. citrifolia. Keputusan kajian ini mencadangkan ekstrak berakua M .citrifolia (sehingga 100 mg/kg) tidak mendatangkan kesan terhadap kualiti sperma dan spermatogenesis mencit.

Matched MeSH terms: Morinda
Fulltext Compounds from the antioxidant active fraction of M. Platytyrea

Nur Fadhilah Mohamad Haris, Mohd Kamal Nik Hasan, Mizaton Hazizul Hasan, Ibtisam Abdul Wahab

Jurnal Sains Kesihatan Malaysia, 2016;14(1):23-29.
MyJurnal

This article discusses on the natural compounds from the ant plant (Myrmecodia species, family: Rubiaceae). The ethyl
acetate (EtOAc) extract from the tuber of M. platytyrea was fractionated by using medium pressure liquid chromatography,
giving eight fractions (F1-F8). Those fractions were evaluated using the 2, 2-diphenyl-1-picrylhydrazyl (DPPH)
assay. Fraction F5 was recorded as potent (EC50 = 21.57 ± 1.40 µg/mL). Then, it was purified by using column
chromatography (CC) (mobile phase = chloroform: EtOAc). From the CC, ten fractions (F5F1-F5F10) were obtained
and compound (1) was isolated from F5F3 via preparative thin layer chromatography (TLC). After spraying with
anisaldehyde-sulphuric reagent, compound (1) gave a green TLC spot (Rf
= 0.65, 100% CHCl3
, multiple development).
The 1
H-Nuclear Magnetic Resonance (NMR) spectroscopy (500 MHz, CDCl3
) was performed to determine the chemical
framework of (1). This compound was identified as morindolide, having an iridoid structure. Meanwhile, the mass
spectra for compounds (2) and (3) were analysed. The data presented the molecular ion at m/z 375 [M-H]- and 255,
suggesting the formulation of 2-(2-methylbutyryl)phloroglucinol glucoside and a flavanone, respectively. From the
literature, compound (1) was firstly isolated from a Chinese natural medicine, the dried root of Morinda officinalis
(family: Rubiaceae). The flavonoids are also included as the biologically active compounds from Myrmecodia. In
short, this is the first occurrence of morindolide from the ant plant.

Matched MeSH terms: Morinda
Fulltext The ethyl acetate fraction of a methanolic extract of unripe noni (Morinda citrifolia Linn.) fruit exhibits a biphasic effect on the dopaminergic system in mice

Pandy V, Narasingam M, Vijeepallam K, Mohan S, Mani V, Mohamed Z

Exp Anim, 2017 Aug 05;66(3):283-291.
PMID: 28450692 DOI: 10.1538/expanim.16-0105

In earlier ex vivo studies, we reported the biphasic effect of a methanolic extract of unripe Morinda citrifolia fruit (MMC) on dopamine-induced contractility in isolated rat vas deferens preparations. The present in vivo study was designed and undertaken to further explore our earlier ex vivo findings. This study examined the effect of the ethyl acetate fraction of a methanolic extract of unripe Morinda citrifolia Linn. fruit (EA-MMC; 5-100 mg/kg, p.o.) on the dopaminergic system using mouse models of apomorphine-induced climbing time and climbing behavior, methamphetamine-induced stereotypy (sniffing, biting, gnawing, and licking) and haloperidol-induced catalepsy using the bar test. Acute treatment with EA-MMC at a low dose (25 mg/kg, p.o.) significantly attenuated the apomorphine-induced climbing time and climbing behavior in mice. Similarly, EA-MMC (5 and 10 mg/kg, p.o.) significantly inhibited methamphetamine-induced stereotyped behavior in mice. These results demonstrated that the antidopaminergic effect of EA-MMC was observed at relatively lower doses (<25 mg/kg, p.o.). On the other hand, EA-MMC showed dopaminergic agonistic activity at a high dose (3,000 mg/kg, p.o.), which was evident from alleviation of haloperidol (a dopamine D2 blocker)-induced catalepsy in mice. Therefore, it is concluded that EA-MMC might possess a biphasic effect on the dopaminergic system, i.e., an antagonistic effect at lower doses (<25 mg/kg, p.o.) and an agonistic effect at higher doses (>1,000 mg/kg, p.o.). However, further receptor-ligand binding assays are necessary to confirm the biphasic effects of M. citrifolia fruit on the dopaminergic system.

Matched MeSH terms: Morinda/chemistry*
Standardized Morinda citrifolia L. and Morinda elliptica L. leaf extracts alleviated fatigue by improving glycogen storage and lipid/carbohydrate metabolism

Osman WNW, Mohamed S

Phytother Res, 2018 Oct;32(10):2078-2085.
PMID: 29993148 DOI: 10.1002/ptr.6151

The antifatigue properties of Morinda elliptica (ME) leaf were compared with Morinda citrifolia (MC) leaf extracts. Sixty Balb/C mice were administered (N = 10): control water, standardized green tea extract (positive control 200 mg/kg body weight [BW]), either 200 or 400 mg MC/kg BW, or either 200 or 400 mg ME/kg BW). The mice performances, biochemical, and mRNA expressions were evaluated. After 6 weeks, the weight-loaded swimming time to exhaustion in the mice consuming 400 mg MC/kg, were almost five times longer than the control mice. The gene expressions analysis suggested the extracts enhanced performance by improving lipid catabolism, carbohydrate metabolism, electron transport, antioxidant responses, energy production, and tissue glycogen stores. The MC and ME extracts enhanced stamina by reducing blood lactate and blood urea nitrogen levels, increasing liver and muscle glycogen reserve through augmenting the glucose metabolism (glucose transporter type 4 and pyruvate dehydrogenase kinase 4), lipid catabolism (acyl-Coenzyme A dehydrogenases and fatty acid translocase), antioxidant (superoxide dismutase 2) defence responses, electron transport (COX4I2), and energy production (PGC1α, NRF1, NRF2, cytochrome C electron transport, mitochondrial transcription factor A, UCP1, and UCP3) biomarkers. The MC (containing scopoletin and epicatechin) was better than ME (containing only scopoletin) or green tea (containing epicatechin and GT catechins) for alleviating fatigue.

Matched MeSH terms: Morinda/chemistry*
Fulltext Hepatoprotective Effects of Morinda citrifolia Leaf Extract on Ovariectomized Rats Fed with Thermoxidized Palm Oil Diet: Evidence at Histological and Ultrastructural Level

Chong CLG, Hussan F, Othman F

Oxid Med Cell Longev, 2019;2019:9714302.
PMID: 31827717 DOI: 10.1155/2019/9714302

Morinda citrifolia (Rubiaceae) or Noni was previously reported to have leaf with broad therapeutic property whereas the fruit was rarely described as medicinal. Ironically, extensive research and review has been done on the fruit and little was known about the therapeutic activity of the leaf as a medicinal food. The aim of this study was to investigate the therapeutic effects of Morinda citrifolia (MC) ethanolic leaf extract on the hepatic structure and function in postmenopausal rats fed with thermoxidized palm oil (TPO) diet. Thirty eight female Sprague Dawley rats were divided into five groups: sham (Sham), ovariectomized (OVX), ovariectomized and treated with simvastatin 10 mg/kg (OVX+ST), ovariectomized and supplemented with low dose MC 500 mg/kg (OVX+MCLD), and ovariectomized and supplemented with high dose MC 1000 mg/kg (OVX+MCHD). All the ovariectomized groups were fed with TPO diet whereas the Sham group was fed with normal diet. Consumption of TPO diet in postmenopausal rats resulted in obesity, significantly elevated (P < 0.05) liver oxidative stress marker; malondialdehyde (MDA), diffuse microvesicular steatosis, and defective mitochondria. Treatment with MC leaf extract prevented hepatic steatosis by significantly increasing (P < 0.05) the liver antioxidant enzyme SOD and GPx, significantly increasing (P < 0.05) ALP, decreasing liver lipids infiltration, preventing mitochondrial damage, and overall maintaining the normal liver histology and ultrastructure. In conclusion, we provided detailed histological and ultrastructural evidence showing hepatoprotective effects of MC leaf extract through its antioxidant mechanism.

Matched MeSH terms: Morinda/chemistry*
Fulltext Combinatorial Cytotoxic Effects of Damnacanthal and Doxorubicin against Human Breast Cancer MCF-7 Cells in Vitro

Aziz MY, Abu N, Yeap SK, Ho WY, Omar AR, Ismail NH, et al.

Molecules, 2016 Sep 14;21(9).
PMID: 27649120 DOI: 10.3390/molecules21091228

Despite progressive research being done on drug therapy to treat breast cancer, the number of patients succumbing to the disease is still a major issue. Combinatorial treatment using different drugs and herbs to treat cancer patients is of major interest in scientists nowadays. Doxorubicin is one of the most used drugs to treat breast cancer patients. The combination of doxorubicin to other drugs such as tamoxifen has been reported. Nevertheless, the combination of doxorubicin with a natural product-derived agent has not been studied yet. Morinda citrifolia has always been sought out for its remarkable remedies. Damnacanthal, an anthraquinone that can be extracted from the roots of Morinda citrifolia is a promising compound that possesses a variety of biological properties. This study aimed to study the therapeutic effects of damnacanthal in combination with doxorubicin in breast cancer cells. Collectively, the combination of both these molecules enhanced the efficacy of induced cell death in MCF-7 as evidenced by the MTT assay, cell cycle, annexin V and expression of apoptosis-related genes and proteins. The effectiveness of doxorubicin as an anti-cancer drug was increased upon addition of damnacanthal. These results could provide a promising approach to treat breast cancer patients.

Matched MeSH terms: Morinda/chemistry
Effects of Damnacanthal and Nordamnacanthal on Proliferation, Apoptosis, and Migration of Oral Squamous Cell Carcinoma Cells

Shaghayegh G, Alabsi AM, Ali-Saeed R, Ali AM, Vincent-Chong VK, Ismail NH, et al.

Asian Pac J Cancer Prev, 2017 Dec 29;18(12):3333-3341.
PMID: 29286228

Cancer is one of the most common causes of death in the developed world, with one-third of people diagnosed with
cancer during their lifetime. Oral cancer commonly occurs involving the buccal mucosa (cheeks), tongue, floor of the
mouth and lip. It is one of the most devastating and disfiguring of malignancies. Morinda citrifolia L., commonly known
as ‘noni’, belongs to the Rubiaceae family. It is native to the Pacific islands, Hawaii, Caribbean, Asia and Australia.
The plant displays broad curative effects in pharmacological studies. Damnacanthal (DAM) and Nordamnacanthal
(NDAM), anthraquinone compounds isolated from the roots of Morinda citrifolia L., has been used for the treatment
of several chronic diseases including cancer. The objectives of this study were to evaluate cytotoxicity, morphological
changes, cell death mode (apoptosis/necrosis), and cell migration induced by DAM and NDAM on the most common
type of oral cancer, oral squamous cell carcinoma (OSCC)cells. Anti-proliferative effects of these compounds against
OSCC cell lines were determined by MTT assay. The mode of cell death was analysed by phase contrast and fluorescent
microscopy as well as flow cytometry. In addition, cell migration was assessed. The results showed that DAM and
NDAM exerted cytotoxicity against OSCC cells with IC50 values of 1.9 to >30 μg/ml after 72 h treatment. Maximum
growth inhibition among the tested cell lines for both compounds was observed in H400 cells, and thus it was selected
for further study. The study demonstrated inhibition of H400 OSCC cell proliferation, marked apoptotic morphological
changes, induction of early apoptosis, and inhibition of cell migration by DAM and NDAM. Therefore, this information
suggests that these compounds from noni have potential for used as anti tumor agents for oral cancer therapy.

Matched MeSH terms: Morinda/chemistry
Chronic toxicity evaluation of Morinda citrifolia fruit and leaf in mice

Mohamad Shalan NAA, Mustapha NM, Mohamed S

Regul Toxicol Pharmacol, 2017 Feb;83:46-53.
PMID: 27871867 DOI: 10.1016/j.yrtph.2016.11.022

Noni (Morinda citrifolia) leaf and fruit are used as food and medicine. This report compares the chronic toxicity of Noni fruit and edible leaf water extracts (two doses each) in female mice. The 6 months study showed the fruit extract produced chronic toxicity effects at the high dose of 2 mg/ml drinking water, evidenced through deteriorated liver histology (hepatocyte necrosis), reduced liver length, increased liver injury marker AST (aspartate aminotransferase) and albumin reduction, injury symptoms (hypoactivity, excessive grooming, sunken eyes and hunched posture) and 40% mortality within 3 months. This hepatotoxicity results support the six liver injury reports in humans which were linked to chronic noni fruit juice consumption. Both doses of the leaf extracts demonstrated no observable toxicity. The hepatotoxicity effects of the M. citrifolia fruit extract in this study is unknown and may probably be due to the anthraquinones in the seeds and skin, which had potent quinone reductase inducer activity that reportedly was 40 times more effective than l-sulforaphane. This report will add to current data on the chronic toxicity cases of Morinda citrifolia fruit. No report on the chronic toxicity of Morinda citrifolia fruit in animal model is available for comparison.

Matched MeSH terms: Morinda/toxicity*; Morinda/chemistry
Damnacanthal: a promising compound as a medicinal anthraquinone

Abu N, Ali NM, Ho WY, Yeap SK, Aziz MY, Alitheen NB

Anticancer Agents Med Chem, 2014 Jun;14(5):750-5.
PMID: 24164045

The Noni fruit, or scientifically known as Morinda citrifolia can be found in various parts of the world, especially in the pacific region. It is a small evergreen bushy-like tree originated from the Rubiaceae family. The plant has been used by polynesians as a medicinal herb for more than 2000 years. A substantial amount of phytochemicals can be found in the roots of this plant. Among all, damnacanthal has been found to be the most interesting, versatile and potent compound. Damnacanthal or chemically known as,3- hydroxy-1-methoxyanthraquinone-2-caboxaldehyde (C16H10O5), appears as pale yellow crystals with a melting point of 210-211 °C. This compound is of particular interest due to its striking pharmacological properties. Damnacanthal was shown to inhibit the oncogene Ras, p56lck tyrosine kinase, NF-KB pathway and induce apoptosis in vitro. This review aims to discuss the biological properties of damnacanthal, specifically on its anti-cancer activity that has been reported.

Matched MeSH terms: Morinda*
Epicatechin and scopoletin rich Morinda citrifolia (Noni) leaf extract supplementation, mitigated Osteoarthritis via anti-inflammatory, anti-oxidative, and anti-protease pathways

Wan Osman WN, Che Ahmad Tantowi NA, Lau SF, Mohamed S

J Food Biochem, 2019 03;43(3):e12755.
PMID: 31353568 DOI: 10.1111/jfbc.12755

The scopoletin (coumarin) and epicatechin (flavonoid) rich Morinda citrifolia L. (MC) Noni leaves are non-toxic (unlike the fruits) and consumed as vegetables. The anti-osteoarthritis effects of the MC leaf extract against joint cartilage degradation and inflammation were investigated through cartilage explant cultures and pre-clinical animal study. Osteoarthritis were induced by intra-articular monosodium iodoacetate injection into the right knee. The extract, scopoletin and epicatechin, suppressed glycosaminoglycan and nitric oxide release from the cartilage explant in the presence of Interleukin-1β. After 28 days, the extract treatment reduced the in vivo serum levels and joint tissues mRNA expressions for joint cartilage degradation, aggrecanase, and collagenase biomarkers. The extract increased the bone formation marker PINP levels, besides improving the articular cartilage structure and chondrocytes cellularity. The extract improved bone formation/repair, subchondral bone structure, strength and integrity, as well as cartilage synthesis by suppressing inflammation, nitric oxide production, joint catabolism by proteases, and oxidative stress. PRACTICAL APPLICATIONS: The scopoletin (coumarin) and epicatechin (flavonoid) rich Morinda citrifolia (Noni) leaves may be used as vegetables, functional food ingredient, or dietary supplements to suppress osteoarthritis progression against joint cartilage degradation and inflammation. The extract, scopoletin, or epicatechin, suppressed glycosaminoglycan, and nitric oxide release from the cartilage. The Morinda citrifolia leaf extract suppressed inflammation, nitric oxide production, tissues catabolism by proteases and oxidative stress to help reduce joint cartilage degradation, besides improving the articular cartilage structure, chondrocytes health, subchondral bone structure, bone formation/repair, and cartilage synthesis.

Matched MeSH terms: Morinda/chemistry*
Fulltext Anticancer Potential of Damnacanthal and Nordamnacanthal from Morinda elliptica Roots on T-lymphoblastic Leukemia Cells

Latifah SY, Gopalsamy B, Abdul Rahim R, Manaf Ali A, Haji Lajis N

Molecules, 2021 Mar 12;26(6).
PMID: 33808969 DOI: 10.3390/molecules26061554

BACKGROUND: This study reports on the cytotoxic properties of nordamnacanthal and damnacanthal, isolated from roots of Morinda elliptica on T-lymphoblastic leukaemia (CEM-SS) cell lines.
METHODS: MTT assay, DNA fragmentation, ELISA and cell cycle analysis were carried out.
RESULTS: Nordamnacanthal and damnacanthal at IC50 values of 1.7 μg/mL and10 μg/mL, respectively. At the molecular level, these compounds caused internucleosomal DNA cleavage producing multiple 180-200 bp fragments that are visible as a "ladder" on the agarose gel. This was due to the activation of the Mg2+/Ca2+-dependent endonuclease. The induction of apoptosis by nordamnacanthal was different from the one induced by damnacanthal, in a way that it occurs independently of ongoing transcription process. Nevertheless, in both cases, the process of dephosphorylation of protein phosphates 1 and 2A, the ongoing protein synthesis and the elevations of the cytosolic Ca2+ concentration were not needed for apoptosis to take place. Nordamnacanthal was found to have a cytotoxic effect by inducing apoptosis, while damnacanthal caused arrest at the G0/G1 phase of the cell cycle.
CONCLUSION: Damnacanthal and nordamnacanthal have anticancer properties, and could act as potential treatment for T-lymphoblastic leukemia.

Matched MeSH terms: Morinda/chemistry*
Fulltext Noni (Morinda citrifolia L.) fruit extract attenuates the rewarding effect of heroin in conditioned place preference but not withdrawal in rodents

Narasingam M, Pandy V, Mohamed Z

Exp Anim, 2016 May 20;65(2):157-64.
PMID: 26744024 DOI: 10.1538/expanim.15-0088

The present study was designed to investigate the effect of a methanolic extract of Morinda citrifolia Linn. fruit (MMC) on the rewarding effect of heroin in the rat conditioned place preference (CPP) paradigm and naloxone-precipitated withdrawal in mice. In the first experiment, following a baseline preference test (preconditioning score), the rats were subjected to conditioning trials with five counterbalanced escalating doses of heroin versus saline followed by a preference test conducted under drug-free conditions (post-conditioning score) using the CPP test. Meanwhile, in the second experiment, withdrawal jumping was precipitated by naloxone administration after heroin dependence was induced by escalating doses for 6 days (3×/ day). The CPP test results revealed that acute administration of MMC (1, 3, and 5 g/kg body weight (bw), p.o.), 1 h prior to the CPP test on the 12th day significantly reversed the heroin-seeking behavior in a dose-dependent manner, which was similar to the results observed with a reference drug, methadone (3 mg/kg bw, p.o.). On the other hand, MMC (0.5, 1, and 3 g/kg bw, p.o.) did not attenuate the heroin withdrawal jumps precipitated by naloxone. These findings suggest that the mechanism by which MMC inhibits the rewarding effect of heroin is distinct from naloxone-precipitated heroin withdrawal.

Matched MeSH terms: Morinda/chemistry*
Fulltext In vitro screening of five local medicinal plants for antibacterial activity using disc diffusion method

Zaidan MR, Noor Rain A, Badrul AR, Adlin A, Norazah A, Zakiah I

Trop Biomed, 2005 Dec;22(2):165-70.
PMID: 16883283 MyJurnal

Medicinal plants have many traditional claims including the treatment of ailments of infectious origin. In the evaluation of traditional claims, scientific research is important. The objective of the study was to determine the presence of antibacterial activity in the crude extracts of some of the commonly used medicinal plants in Malaysia, Andrographis paniculata, Vitex negundo, Morinda citrifolia, Piper sarmentosum, and Centella asiatica. In this preliminary investigation, the leaves were used and the crude extracts were subjected to screening against five strains of bacteria species, Methicillin Resistant Staphylococcus aureus (MRSA), Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa and Escherichia coli, using standard protocol of Disc Diffusion Method (DDM). The antibacterial activities were assessed by the presence or absence of inhibition zones and MIC values. M. citrifolia, P. sarmentosum and C. asiatica methanol extract and A. paniculata (water extract) have potential antibacterial activities to both gram positive S. aureus and Methicillin Resistant S. aureus (MRSA). None of the five plant extracts tested showed antibacterial activities to gram negative E. coli and K. pneumoniae, except for A. paniculata and P. sarmentosum which showed activity towards P. aeruginosa. A. paniculata being the most potent at MIC of 2 g/disc. This finding forms a basis for further studies on screening of local medicinal plant extracts for antibacteria properties.

Matched MeSH terms: Morinda/chemistry
Morinda citrifolia leaf enhanced performance by improving angiogenesis, mitochondrial biogenesis, antioxidant, anti-inflammatory & stress responses

Mohamad Shalan NA, Mustapha NM, Mohamed S

Food Chem, 2016 Dec 01;212:443-52.
PMID: 27374554 DOI: 10.1016/j.foodchem.2016.05.179

Morinda citrifolia fruit, (noni), enhanced performances in athletes and post-menopausal women in clinical studies. This report shows the edible noni leaves water extract enhances performance in a weight-loaded swimming animal model better than the fruit or standardized green tea extract. The 4weeks study showed the extract (containing scopoletin and epicatechin) progressively prolonged the time to exhaustion by threefold longer than the control, fruit or tea extract. The extract improved (i) the mammalian antioxidant responses (MDA, GSH and SOD2 levels), (ii) tissue nutrient (glucose) and metabolite (lactate) management, (iii) stress hormone (cortisol) regulation; (iv) neurotransmitter (dopamine, noradrenaline, serotonin) expressions, transporter or receptor levels, (v) anti-inflammatory (IL4 & IL10) responses; (v) skeletal muscle angiogenesis (VEGFA) and (v) energy and mitochondrial biogenesis (via PGC, UCP3, NRF2, AMPK, MAPK1, and CAMK4). The ergogenic extract helped delay fatigue by enhancing energy production, regulation and efficiency, which suggests benefits for physical activities and disease recovery.

Matched MeSH terms: Morinda*
Development of biodegradable sustained-release damnacanthal nanocapsules for potential application in in-vitro breast cancer studies

Mohd MR, Ariff TM, Mohamad N, Abdul Latif AZ, Wan Nik WMN, Mohamed A, et al.

Pak J Pharm Sci, 2019 Sep;32(5):2155-2162.
PMID: 31813882

The "noni" species of Morinda citrifolia L., is using in traditional medicine in the tropical country for over 2000 years. Noni fruit has come from the Morinda citrifolia tree which is called Rubiaceae, and it is from the coffee family. It is a perennial herb whose ripe fruit has a robust butyric acid smell and flavor. Recently scientists have proven that this fruit has antioxidant and antibiotic properties in vitro. An anthraquinone, damnacanthal, is one of the constituents of Morinda citrifolia. It has been demonstrated to have anti-cancer properties. Damnacanthal has low water solubility and low bioavailability. Formulating of damnacanthal into the biodegradable nanocapsule drug delivery system may increase its bioavailability. Various formulations of damnacanthal would be developed to enable the selection of a dosage form that could offer the provision of the anti-cancer bioactive substance with suitable sustained- or controlled release properties. The efficiency of extraction of damnacanthal will be compared using both conventional and traditional method. Both the damnacanthal and an anthraquinone active compounds extracted from noni roots, are currently being studied in the context of anti-cancer study. Soon, the medical values, bioactivities and nutritional of this fruit can be assessed, especially its anti-cancer activity, this fruit extract could play an outstanding economic role in Malaysia and other tropical countries.

Matched MeSH terms: Morinda/chemistry
Metastasized lung cancer suppression by Morinda citrifolia (Noni) leaf compared to Erlotinib via anti-inflammatory, endogenous antioxidant responses and apoptotic gene activation

Lim SL, Mustapha NM, Goh YM, Bakar NA, Mohamed S

Mol Cell Biochem, 2016 May;416(1-2):85-97.
PMID: 27106908 DOI: 10.1007/s11010-016-2698-x

Metastasized lung and liver cancers cause over 2 million deaths annually, and are amongst the top killer cancers worldwide. Morinda citrifolia (Noni) leaves are traditionally consumed as vegetables in the tropics. The macro and micro effects of M. citrifolia (Noni) leaves on metastasized lung cancer development in vitro and in vivo were compared with the FDA-approved anti-cancer drug Erlotinib. The extract inhibited the proliferation and induced apoptosis in A549 cells (IC50 = 23.47 μg/mL) and mouse Lewis (LL2) lung carcinoma cells (IC50 = 5.50 μg/mL) in vitro, arrested cancer cell cycle at G0/G1 phases and significantly increased caspase-3/-8 without changing caspase-9 levels. The extract showed no toxicity on normal MRC5 lung cells. Non-small-cell lung cancer (NSCLC) A549-induced BALB/c mice were fed with 150 and 300 mg/kg M. citrifolia leaf extract and compared with Erlotinib (50 mg/kg body weight) for 21 days. It significantly increased the pro-apoptotic TRP53 genes, downregulated the pro-tumourigenesis genes (BIRC5, JAK2/STAT3/STAT5A) in the mice tumours, significantly increased the anti-inflammatory IL4, IL10 and NR3C1 expression in the metastasized lung and hepatic cancer tissues and enhanced the NFE2L2-dependent antioxidant responses against oxidative injuries. The extract elevated serum neutrophils and reduced the red blood cells, haemoglobin, corpuscular volume and cell haemoglobin concentration in the lung cancer-induced mammal. It suppressed inflammation and oedema, and upregulated the endogenous antioxidant responses and apoptotic genes to suppress the cancer. The 300 mg/kg extract was more effective than the 50 mg/kg Erlotinib for most of the parameters measured.

Matched MeSH terms: Morinda/chemistry*

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