Aakanksha Pant

Beta-caryophyllene modulates expression of stress response genes and mediates longevity in Caenorhabditis elegans

Beta-caryophyllene (BCP) is a natural bicyclic sesquiterpene and is a FDA approved food additive, found as an active ingredient in essential oils of numerous edible plants. It possesses a wide range of biological activities including anti-oxidant, anti-inflammatory, anti-cancerous and local anesthetic actions. We used the well established Caenorhabditis elegans model system to elucidate the stress modulatory and lifespan prolonging action of BCP. The present study for the first time reports the lifespan extension and stress modulation potential of BCP in C. elegans. Upon evaluation, it was found that 50μM dose of BCP increased the lifespan of C. elegans by over 22% (P≤0.0001) and significantly reduced intracellular free radical levels, maintaining cellular redox homeostasis. Moreover, the results suggest that BCP modulates feeding behavior, pharyngeal pumping and body size effectively. Further, this compound also exhibited significant reduction in intestinal lipofuscin levels. In the present investigation, we have predicted possible biological molecular targets for BCP using molecular docking approaches and BCP was found to have interaction with SIR-2.1, SKN-1 and DAF-16. The prediction was further validated in vivo using mutants and transgenic strains unraveling underlying genetic mechanism. It was observed that BCP increased lifespan of mev-1 and daf-16 but failed to augment lifespan in eat-2, sir-2.1 and skn-1 mutants. Relative quantification of mRNA demonstrated that several genes regulating oxidative stress, xenobiotic detoxification and longevity were modulated by BCP treatment. The study unravels the involvement of multiple signaling pathways in BCP mediated lifespan extension.

Curcumin and β-caryophellene attenuate cadmium quantum dots induced oxidative stress and lethality in Caenorhabditis elegans model system

Curcumin (CUR) and β-caryophellene (BCP) are well known bioactive phytomolecules which are known to reduce oxidative stress in living organisms. Therefore, the present study was envisaged to explore the possible effects of CUR and BCP in suppression of cadmium quantum dots (CdTe QDs) induced toxicity in Caenorhabditis elegans. CdTe QD are luminescent nanoparticles extensively exploited for in vivo imaging, but long term bioaccumulation confer deleterious effects on living organisms. The 24-h LC50 and LC100 of CdTe QD were found to be 18.40 μg/ml and 100 μg/ml respectively. The CdTe QD exposure elevated HSP-16.2 expression mediating induction of the stress response. The CdTe QD lethality was due to increment in ROS and decline in SOD and GST expression. The present study demonstrates improved survival in BCP (50 μM) and CUR (20 μM) treated worms by over 60% (P<0.01) and 50% (P<0.029) in CdTe QD (100 μg/ml) exposed worms. Furthermore, BCP and CUR attenuate oxidative stress triggered by QD. The present study for the first time demonstrates CdTe QD toxicity remediation via BCP and CUR. The future investigations can unravel underlying protective effects of phytomolceules for remediating cyotoxicolgical effects of QDs.

Specioside ameliorates oxidative stress and promotes longevity in Caenorhabditis elegans

Specioside (6-O-coumaroylcatalpol) is an iridoid glucoside which possesses multifunctional activities viz. analgesic, antidyspeptic, astringent, liver stimulating and wound healing properties. The present study for the first time delineates stress alleviating and lifespan prolonging action of specioside (SPC), isolated from Stereospermum suaveolens in the free living, multicellular nematode model Caenorhabditis elegans. A strong correlation between lifespan extension and stress modulation in adult worms was established in a dose dependent manner. The dietary intake of this phytomolecule elevated juglone induced oxidative and heat induced thermal stress tolerance in C. elegans. On evaluation, it was found that 25 μM dose of SPC significantly extended lifespan by 15.47% (P≤0.0001) with reduction in stress level. Furthermore, SPC enhanced mean survival in mev-1 mutant suggesting its oxidative stress reducing potential. Furthermore, SPC augmented stress modulatory enzymes superoxide dismutase (SOD) and catalase (CAT) level in C. elegans. Altogether, these findings broaden current perspectives concerning stress alleviating potentials of SPC and have implications in development of therapeutics for curing age related disorders.

Genetic revelation of hexavalent chromium toxicity using Caenorhabditis elegans as a biosensor

The interaction of heavy metals such as hexavalent chromium, Cr (VI) with the environment drastically influences living organisms leading to an ecological imbalance. Caenorhabditis elegans, a saprophytic nematode having 60–80% homology with human genes offers a distinct advantage to be used as a biosensor for the appraisal of heavy metal-induced environmental toxicity and risk monitoring. The present study examines the toxicity effects of K2Cr2O7 as Cr (VI) on stress-related gene expression and morphometric parameters of C. elegans under in vitro conditions to identify genetic markers for environmental pollution. Alterations in growth and modified gene expression were observed in Cr (VI)-exposed N2 worms. The 24-h median lethal concentration for Cr (VI) was observed as 158.5 mgl−1. Use of the responses of stress-related gene expression suggests that C. elegans can be used as an efficient biosensor for figuring out the precise route of Cr (VI)-induced environmental toxicity in a quick, simple, and inexpensive manner.

Acacetin 7-O-α-l-rhamnopyranosyl (1–2) β-D-xylopyranoside Elicits Life-span Extension and Stress Resistance in Caenorhabditis elegans

The advancements in the field of gerontology have unraveled the signaling pathways that regulate life span, suggesting that it might be feasible to modulate aging. To this end, we isolated a novel phytomolecule Acacetin 7-O-α-l-rhamnopyranosyl (1-2) β-D-xylopyranoside (ARX) from Premna integrifolia and evaluated its antiaging effects in Caenorhabditis elegans The spectral data analysis revealed the occurrence of a new compound ARX. Out of the three tested pharmacological doses of ARX, viz. 5, 25, and 50 µM, the 25-µM dose was able to extend life span in C. elegans by more than 39%. The present study suggests that ARX affects bacterial metabolism, which in turn leads to dietary restriction (DR)-like effects in the worms. The effect of ARX on worms with mutations (mev-1, eat-2, sir-2.1, skn-1, daf-16, and hsf-1) indicates that ARX-mediated life-span extension involves mechanisms associated with DR and maintenance of cellular redox homeostasis. This study is the first time report on longevity-promoting activity of ARX in C. elegans mediated by stress and DR-regulating genes. This novel phytomolecule can contribute in designing therapeutics for managing aging and age-related diseases.

Verminoside mediates life span extension and alleviates stress in Caenorhabditis elegans

Abstract The discovery of bioactive molecules modulating aging in living organism promotes development of natural therapeutics for curing age-related afflictions. The progression in age-related disorders can be attributed to increment in intracellular reactive oxygen species (ROS) and oxidative stress level. To this end, we isolated an iridoid verminoside (VMS) from Stereospermum suaveolens (Roxb.) DC. and evaluated its effect on Caenorhabditis elegans. The present study delineates VMS-mediated alteration of intracellular ROS, oxidative stress, and life span in C. elegans. The different tested doses of VMS (5 μM, 25 μM, and 50 μM) were able to enhance ROS scavenging and extend mean life span in C. elegans. The maximal life span extension was observed in 25 μM VMS, that is, 20.79% (P < 0.0001) followed by 9.84% (P < 0.0001) in 5 μM VMS and 8.54% (P < 0.0001) in 50 μM VMS. VMS was able to alleviate juglone-induced oxidative stress and enhanced thermotolerance in worms. The stress-modulating and ROS-scavenging potential of VMS was validated by increment in mean survival by 29.54% (P < 0.0001) in VMS-treated oxidative stress hypersensitive mev-1 mutant strain. Furthermore, VMS modulates expression of DAF-16 (a FoxO transcription factor) promoting stress resistance and longevity. Altogether, our results suggest that VMS attenuates intracellular ROS and stress (oxidative and thermal) level promoting longevity. The longevity and stress modulation can be attributed to VMS-mediated alterations in daf-16 expression which regulates insulin signaling pathway. This study opens doors for development of phytomolecule-based therapeutics for prolonging life span and managing age-related severe disorders.

Ocimum Species: A Longevity Elixir

Aging is a major risk factor associated with the period of morbidity and pain at a later stage of life. Although the average age for initiation of morbidity has delayed, chronic diseases like hypertension, cancer, diabetes, and neurodegenerative disorders are still prevalent in affluent aging societies leading to death. Therefore, studying dietary interventions and pathology of aging can prove as an essential strategy for achieving healthy aging. The recent researches demonstrated an association of aging with remarkable elevation in intracellular reactive oxygen species (ROS) and stress. The plant-based molecules have successfully modulated lifespan and stress level across various species. These phytomolecules are secondary plant metabolites which play a major role in plant defence network and are synthesized as side tracks of plant’s primary metabolism. Despite the recently discovered potential of some phytomolecules in alleviating age-related stress, antiaging and stress modulatory potential of most of them is still unraveled. The natural dietary intervention modulating lifespan and health span in model organisms should be vastly studied for improving later life health. The free-living soil nematode, Caenorhabditis elegans, provides a unique and expedient platform for studying pharmacological interventions and dissecting the genetic mechanism underlying aging. The present chapter highlights the medicinal and therapeutic potential of the various Ocimum species which is commonly known as the “Queen of the herbs.” The antioxidant and antiaging potential of phytomolecules and extracts derived from this genus is thoroughly reported. Basil is the rich repository of many bioactive molecules such as monoterpenes, sesquiterpenes, phenylpropanoids, anthocyanins, and phenolic acids; therefore, the longevity-promoting potential of this herb is highlighted in the present chapter. Furthermore, special attention is given to the employment of C. elegans model system for screening various phytochemicals isolated from Ocimum spp.

Diseases of medicinal and aromatic plants, their biological impact and management

With increasing interest in natural products of plant origin for medicinal and health care benefits there is added emphasis on the quality of the source raw material. In most cases the vegetative tissues and organs are the source of the required raw material. However, such tissues/organs may become infested/susceptible to many diseases causing deterioration of the quality of the desired economic product and loss of genetic resources. Considerable progress has been made with respect to the identification of disease causing organisms, and their pathogenic impact at organ, cellular and biochemical level. This review focuses on various diseases caused by bacteria, fungi, nematodes, viruses and phytoplasmas threatening the yield, biomass, bioactive potential of medicinal and aromatic plants of the sub-tropics. Several studies suggest that management of diseases through biological measures is more effective to check multiple diseases. Necessary management strategies for efficient disease management to realize quality raw material and enhanced metabolite productive potential have been outlined.