Standardized Kaempferia parviflora Extract Inhibits Intrinsic Aging Process in Human Dermal Fibroblasts and Hairless Mice by Inhibiting Cellular Senescence and Mitochondrial Dysfunction

Abstract

Intrinsic skin aging is a complex biological phenomenon mainly caused by cellular senescence and mitochondrial dysfunction. This study evaluated the inhibitory effect of Kaempferia parviflora Wall ex. Baker ethanol extract (KPE) on H2O2-stimulated cellular senescence and mitochondrial dysfunction both in vitro and in vivo. KPE significantly increased cell growth and suppressed senescence-associated β-galactosidase activation. KPE inhibited the expression of cell-cycle inhibitors (p53, p21, p16, and pRb) and stimulated the expression of cell-cycle activators (E2F1 and E2F2). H2O2-induced hyperactivation of the phosphatidylinositol 3-kinase/protein kinase B (AKT) signaling pathway was suppressed by KPE through regulated expression of forkhead box O3a (FoxO3a) and mammalian target of rapamycin (mTOR). KPE attenuated inflammatory mediators (interleukin-6 (IL-6), IL-8, nuclear factor kappa B (NF-κB), and cyclooxygenase-2 (COX-2)) and increased the mRNA expression of PGC-1α, ERRα, NRF1, and Tfam, which modulate mitochondrial biogenesis and function. Consequently, reduced ATP levels and increased ROS level were also reversed by KPE treatment. In hairless mice, KPE inhibited wrinkle formation, skin atrophy, and loss of elasticity by increasing the collagen and elastic fibers. The results indicate that KPE prevents intrinsic aging process in hairless mice by inhibiting cellular senescence and mitochondrial dysfunction, suggesting its potential as a natural antiaging agent.

Inhibitory effect of vitamin C on intrinsic aging in human dermal fibroblasts and hairless mice

“…PCR amplification was conducted in a Gene Amp PCR System 2700 (Applied Biosystems, Foster City, CA, USA). Primers were designed according to Primer-BLAST (http://www.ncbi.nlm.nih.gov/tools/primer-blast/) and our previous study [13]. The following primer pairs (Bioneer, Daejeon, Korea) were used: human p53 (forward, 5 0 -ACA CGC TTC CCT GGA TTG G-3 0 ; reverse, 5 0 -CTG GCA TTC TGG GAG CTT CA-3 0 ), human p21 (forward, 5 0 -GTC AGT TCC TTG TGG AGC CG-3 0 ; reverse, 5 0 -GGA AGG TAG AGC TTG GGC AG-3 0 ), human p16 (forward, 5 0 -GGG TCC CAG TCT GCA GTT AAG-3 0 ; reverse, 5 0 -CAG TAG CAT CAG CAC GAG GG-3 0 ), human pRb (forward, 5 0 -TTT ATT GGC GTG CGC TCT TG-3 0 ; reverse, 5 0 -CAG TTG GTC CTT CTC GGT CC-3 0 ), human E2F1 (forward, 5 0 -CCG CCA TCC AGG AAA AGG TG-3 0 ; reverse, 5 0 -GCT ACG AAG GTC CTG ACA CG-3 0 ), human E2F2 (forward, 5 0 -GAC TAG AGA GCG AGC CGC AA-3 0 ; reverse, 5 0 -GAG CAG AGA GCA GCG CTT AG-3 0 ), human SIRT1 (forward, 5 0 -ACC GAG ATA ACC TTC TGT TCG-3 0 ; reverse, 5 0 -CAC CCC AGC TCC AGT TAG AA-3 0 ), human IL-6 (forward, 5 0 -ATG AGG AGA CTT GCC TGG TG-3 0 ; reverse, 5 0 -ACA ACA ATC TGA GGT GCC CA-3 0 ), human IL-8 (forward, 5 0 -CCA GGA AGA AAC CAC CGG AA-3 0 ; reverse, 5 0 -CCT CTG CAC CCA GTT TTC CT-3 0 ), human GAPDH (forward, 5 0 -CTC CTG TTC GAC AGT CAG CC-3 0 ; reverse, 5 0 -TCG CCC CAC TTG ATT TTG GA-3 0 ).…”

“…Aged skin dermis shows a destruction in the elastic fiber network, resulting in decreased skin elasticity [22]. In order to evaluate the effect of vitamin C on elastic fibers in aged skin, we used a Verhoeff-van Gieson's staining which is a method to evaluate the elastic fibers in skin [12,13,23]. As compared to the MA mice group, vitamin C administration (50 or 200 mg/kg/day) increased elastic fibers (Fig.…”

Glucose Tolerance Test and Pharmacokinetic Study of Kaempferia parviflora Extract in Healthy Subjects

“…Ethnopharmacologically, the plant rhizomes have been traditionally used in folk medicine for centuries for longevity promotion, anti-fatigue, appetite induction, male sexual stimulation, anti-stomachache, and laxative [2,3]. KP extract and its major constituents have been reported to confer several health beneficial effects through in vitro and animal studies, including aphrodisiac activity [4,5,6,7], anti-inflammation [8], anti-cancer [9,10], cardioprotection [11,12], anti-peptic ulcer [13], antimicrobial [14], anti-allergy [15], anti-mutagenicity [16], anti-depression [17], anti-cholinesterase activity [17,18], prevention in the brain from valproic acid-induced impairment of spatial memory [19], inhibition of intrinsic aging processes [20], anti-osteoporosis [21], reduction of pain threshold and severity of osteoarthritis [22], anti-obesity and prevention of obesity-induced dermatopathy [23,24], inhibition of fat accumulation and muscle atrophy [25], increased whole-body energy expenditure [26], improvement of obesity and insulin resistance [27], and promotion of the differentiation of brown adipose tissue [28,29]. In terms of antidiabetic activity, the ethanol extract of KP was reported to decrease blood glucose in streptozocin-induced diabetic rats [30].…”

Kaempferia parviflora and Its Methoxyflavones: Chemistry and Biological Activities

“…KP extract also increases cell growth and inactivates senescence-related β -galactosidase through inhibition of cell cycle inhibitors (p16, p21, p53, and pRb) and upregulation of cell cycle activators (E2F1 and E2F2). H 2 O 2 -induced upregulation of PI3K/AKT signaling pathways is also attenuated by KP extract through activation of forkhead box O3a (FoxO3a) and mammalian target of rapamycin (mTOR) [58] (Table 1).…”