C H A P T E R

10
Herbs and Spices in Aging
Suhaila Mohamed
Institute of BioScience, Universiti Putra Malaysia, Serdang, Selangor, Malaysia

List of Abbreviations oxidative stress often results in degenerative chronic com-

plications and premature aging affecting the eyes, heart,
ABETA  β-amyloid
AGEs  advanced glycation endproducts liver, blood vessels, nerves and kidneys. Aging animals
AMD  age-related macular degeneration show increased lipid peroxidation activities and decreased
AP-1  activator protein 1 antioxidant levels in the kidneys, skins, lenses, hearts and
APP  amyloid precursor protein aortas.1 Circulating lipid peroxides can initiate atheroscle-
ATP  adenosine triphosphate
rosis under oxidative stress. Prolonged oxidative stress
BCL2  gene encoding apoptosis regulator proteins
COX cyclooxygenase increases protein glycation and the pathologic advanced
DNA  deoxyribonucleic acid glycation endproducts (AGEs) in organ tissues; some
FGF  fibroblast growth factor herbs and spices contain potent antiglycation compounds.
GFAP  glial fibrillary acidic protein The AGEs occur on intra- and extracellular proteins, lip-
HIV  human immunodeficiency virus
ids and nucleic acids; they not only cause overproduc-
IL interleukin
iNOS  inducible nitric oxide synthase tion of free radicals, which are damaging to the cells, but
L-NAME  l-N-arginine methyl ester used to induce nitric oxide (NO) also change intracellular signaling and gene expression –
deficiency in rats resulting in a release of pro-inflammatory molecules and
LOX lipooxygenase free radicals that cause lesions in tissues and organs. Over
MDA malondialdehyde
42 herbs and spices have antiglycation properties2 and
ncRNAs  noncoding RNAs
NFκB  nuclear factor-kappaB their antiglycation properties are highly correlated to their
NO  nitric oxide total content of polyphenols.3 These antiglycating herbs
RNA  ribonucleic acid and spices include Allium sativum, Zingiber officinale, Thy-
RPE  retinal pigment epithelial mus vulgaris, Petroselinum crispum, Murraya koenigii Spreng,
SBP  systolic blood pressure
Mentha piperita L., Curcuma longa L., Allium cepa L., Allium
SOD  superoxide dismutase
TNF  tumor necrosis factor fistulosum and Coriandrum sativum L.
UPP  ubiquitin–proteasome pathway The ubiquitin–proteasome pathway (UPP) selectively
UVB  ultraviolet B degrades aberrant proteins to appropriately remove
VEGF  vascular endothelial growth factor potential cytotoxic, damaged or abnormal proteins
linked to aging and degenerative diseases. Age, oxida-
tive-stress-induced impairment or overburdening of the
INTRODUCTION UPP hinders the removal of abnormal proteins from the
tissues. Certain herbs and spices (examples: turmeric,
Antioxidative herbs and spices can help to slow down
cinnamon and herbs containing 3,5-dicaffeoyl quinic
ailments related to aging in animal models by reducing
acid) help to prevent health degeneration by enhancing
tissue oxidative stress. Many herbs and spices are used
or preserving UPP function or reducing the UPP burden.
as traditional medicines for infections, various injuries,
repelling insects, toothache, ulcers, wounds, arthritis,
rheumatism, sprains, asthma, allergies, bronchitis, colic, SPICES
dyspepsia, nausea and minor infections. They have diges-
tive, mild anesthetic, stimulant, mild irritant, vasodila- Spice is defined as any aromatic or pungent plant
tive, antinausea, antibacterial, antifungal, antilisteric, substance used to flavor food. Some food season-
antioxidative and anti-inflammatory properties.1 Chronic ing spices help to improve plasma glucose, glucose

Aging 99
http://dx.doi.org/10.1016/B978-0-12-405933-7.00010-X Copyright © 2014 Suhaila Mohamed. Published by Elsevier Inc. All rights reserved.
100
Normal rats: normal
myocardial fibers in N and
NC rats [H&E × 100].
FIGURE 10.1  Histological evidence of the protective effects of cloves on oxidatively stressed diabetic rat’s heart. 1 N, normal ats; NC, Normal
rats with cloves in their diet; D, Diabetic rats; DC, Diabetic rats with cloves in their diet.
FIGURE 10.2  Histological evidence of the protec-
tive effects of antioxidative spice (clove) on oxidatively
stressed diabetic rats’ lenses. Reproduced with per-
mission from reference 1.
metabolism and the lipid profile of hyperinsulinemic
mammals. The modes of action include improving
insulin-sensitivity and reducing oxidative stress in
the tissues. Some culinary herbs and spices effectively
inhibit protein glycation, and the most potent inhibi-
tors reported were cloves, ground Jamaican allspice
and cinnamon extracts.1,4
Clove
Clove, and some other culinary herbs and spice
extracts, apparently have insulin-enhancing activity or
cause increases in insulin sensitivity.5 Consumption of
cloves (equivalent to about 1g cloves/day for humans)
gradually lowers fasting blood glucose levels.1 Clove
oil helps to modulate physiologic responses in aging
rodents.6,7 The eugenol and eugenyl acetate in cloves
are antioxidative. Eugenol dose dependently binds to
membranes, thus stabilizing them and protecting them
against free radical attack.8 Eugenol inhibits lipid oxi-
dation and helps to limit structural changes to various
tissues, such as the heart, kidney and liver.1,9 Eugenol
inhibits histamine release from mast cells to reduce
hypersensitivity10 besides having anti-anaphylactic and
antispasmodic properties.11 Cloves inhibit oxidative
2.  ANTIOXIDANTS AND AGING
10.  HERBS AND SPICES IN AGING
Diabetic rats: vacuolation Diabetes + cloves: DC rats
and fibrosis in D rats showed reduced fibrosis
[H&E × 100]. [H&E × 100].
Normal lenses of normal rats and diabetic rats Cataract in the lens of diabetic rats [H&E ×
supplemented with clove. 100].
tissue damage and cataract formation in the eye lens of
rats.1 Cataractogenesis is caused by glucose diffusion
into the lens, increased sorbitol levels, altered membrane
permeability, loss of glutathione, decreased amino acid
levels and decreased protein synthesis. Besides protect-
ing the eye lens, dietary cloves also protect against dam-
age to the heart (Figs 10.1 and 10.2).
Turmeric
Turmeric contains the antioxidative polyphenol cur-
cumin (diferuloylmethane), which has anti-inflamma-
tory, antiproliferative, anticancer and anti-angiogenic
activities. Curcumin regulates the expression of genes
related to apoptosis, tumor suppression, cell-cycle
arrest, transcription factor, angiogenesis and metasta-
sis.12 Curcumin ameliorates various chronic illnesses,
linked to free radical damage, affecting the eyes, lungs,
liver, kidneys and the gastrointestinal and cardiovascu-
lar systems. Curcumin modulates signaling molecules,
including inflammatory molecules, transcription fac-
tors, enzymes, protein kinases, protein reductases,
carrier proteins, cell-survival proteins, drug resistance
proteins, adhesion molecules, growth factors, receptors,
cell-cycle regulatory proteins, chemokines, DNA, RNA
 Spices
and metal ions, important in oxidation, obesity, neu-
rologic and psychiatric disorders and cancer.12 Addi-
tionally, curcumin has antibacterial, chemopreventive,
chemotherapeutic, antinociceptive, antiparasitic and
antimalarial properties13 and it blocks HIV replication.
Curcumin is non-toxic in normal cells and kills only
tumor cells.14 Turmeric and curcumin prevented oxi-
dative stress in diabetic mammals without changing
blood sugar levels.15 Turmeric and curcumin benefit
acute and chronic diseases associated with enhanced
inflammation (such as arteriosclerosis, cancer, respi-
ratory, hepatic, pancreatic, intestinal and gastric dis-
eases, neurodegeneration and degenerative diseases)16
by inhibiting inflammation mediators such as NFKB,
cyclooxygenase-2 (COX-2), lipooxygenase (LOX) and
inducible nitric oxide synthase (iNOS). Curcuminoids,
like many other polyphenols, have antioxidant effects
greater than those of vitamins,17 and they induce
enzymes of the glutathione-linked detoxification path-
ways.18 Phase I clinical trials have shown that tur-
meric is safe, even at high doses (12 g/day), in humans
because of its poor bioavailability, poor absorption,
rapid metabolism and rapid systemic elimination.19
Curcumin prevents degenerative disease by modulat-
ing (i) several cell-signaling pathways at multiple levels,
(ii) cellular enzymes, e.g. cyclooxygenase and glutathi-
one S-transferases, (iii) the immune system, (iv) angio-
genesis, (v) cell–cell adhesion, (vi) gene transcription
and (vii) apoptosis in preclinical cancer models. Despite
the low systemic bioavailability following oral dosing,
biologically active levels in the gastrointestinal tract
have been reached.20
Turmeric is a promising herb for the prevention of
age-related Alzheimer’s disease. Curcumin significantly
lowered oxidized proteins and proinflammatory cyto-
kines in rodents’ brains. Low doses of curcumin reduced
the astrocytic marker (GFAP-glial fibrillary acidic pro-
tein), insoluble β-amyloid (ABETA), soluble ABETA and
plaque burden by almost 50%, without reducing levels
of amyloid precursor protein (APP) in the membrane
fraction. These effects were not observed with a high
dose of curcumin. Microgliosis was suppressed in neu-
ronal layers but not near the plaques.21
Turmeric and curcumin inhibited the expression of
vascular endothelial growth factor (VEGF) in rats,22 and
inhibited endothelial cell proliferation in vivo.23 Hence,
curcumin may be protective against various neovascu-
larization-related diseases, stimulated by VEGF, such as
cancer and obesity. Turmeric and curcumin prevented
cataract development in rodents, even though it is not
antihyperglycemic. Turmeric was more effective than
curcumin in countering oxidative stress15 when com-
paring the rates for changes in (i) lipid peroxidation,
(ii) reduced glutathione, (iii) protein carbonyl content,
(iv) antioxidant enzyme activities, (v) osmotic stress
2.  ANTIOXIDANTS AND AGING
101
(assessed by polyol pathway enzymes), and (vi) aggre-
gation or insolubilization of lens proteins induced by
hyperglycemia.
Dietary curcumin is effective only in very low amounts
(0.002%), but not at high levels (above 0.01%). Curcumin,
at a low level (0.002%), inhibited oxidation, glycation,
lipid peroxidation, AGE-fluorescence and protein aggre-
gation. Under hyperglycemic conditions, higher levels
of dietary curcumin (0.01%) showed the opposite effect
of being pro-oxidative, enhancing AGE formation and
protein aggregation. However, feeding curcumin to nor-
mal rats at up to a 0.01% level did not cause any changes
in morphology or biochemical parameters24 because of
its poor bioavailability.
The mechanisms for curcumin protection against
lipid peroxidation or galactose-induced oxidative stress
are (i) through glutathione S-transferase isozyme induc-
tion25 and (ii) by decreasing apoptosis in cells.18 Dietary
curcumin improved tissue morphology, physiology,
gene expression, tissue structure and function in animal
models of visual degeneration,16,25–27 oxidative damage
and Alzheimer disease.21 Curcumin may benefit vari-
ous degenerative diseases caused by protein trafficking
defects such as diabetes, cancer and Alzheimer’s dis-
ease. Treatment of COS-7 cells with curcumin results in
dissociation of mutant protein aggregates and decreased
endoplasmic reticulum stress.27
Excess free radical generation caused Ca2+ ATPase
inactivation, leading to Ca2+ accumulation and cal­
pain-mediated proteolysis. Pretreatment with cur-
cumin, but not simultaneous or post-treatment, led
to a decrease in oxidative stress and also rescued the
(selenium-induced) increase in Ca2+ and inhibition of
Ca2+ ATPase activity in the eye lens.28 Curcumin medi-
ates its effects through the inhibition of transcription
factors (NFκB, AP-1), enzymes (COX-1, COX-2, LOX),
cytokines (TNF, IL-1, IL-6) and the down-regulation
of anti-apoptotic genes (BCL2, BCL2L1). These effects
are helpful for various oxidative-stress -and inflam-
mation-related degenerative diseases such as can-
cers, Alzheimer’s disease, cardiovascular ailments,
arthritis, alcohol-induced liver injury and multiple
sclerosis. Curcumin inhibited the increase in tissue
epithelial cells’ pigments exclusively by inducing cas-
pase-3/7-dependent but not via caspase-8-dependent
cell death and necrosis.29
Cinnamon, Black Pepper, Cumin
Cinnamon extract helped safeguard against tissue
changes by minimizing protein aggregation, preventing
glycation and oxidative stress in fructose-fed rodents.
Cumin, ginger, green tea, cinnamon and black pepper, at
1.0 mg/ml, inhibited the formation, in vitro, of advanced
glycation endproducts (AGE).2
102 10.  HERBS AND SPICES IN AGING

Piperine, from black pepper, effectively retarded HERBS

memory impairment and neurodegeneration in the
brain of an Alzheimer’s disease animal model. Pip-
erine inhibited lipid peroxidation as well as acetyl-
cholinesterase, and had neurotrophic effects in the
hippocampus.30
Ginger (Zingiber officinalis)
Ginger is known to be carminative, thermogenic,
anti-inflammatory, antioxidative and stimulating. It is
used traditionally for dyspepsia, gastroparesis, slow
motility symptoms, constipation, nausea, coughs, colds
or flu, vomiting, colic, pain relief, rheumatoid arthri-
tis, osteoarthritis and joint and muscle injury. Dietary
ginger has antiglycating properties, inhibits the polyol
pathway, and is antihyperglycemic. Ginger signifi-
cantly inhibited the formation of various AGE prod-
ucts, including carboxymethyl lysine.31 Dietary ginger
delayed cataract onset and progression in rats. Dietary
zerumbone from zerumbet ginger dose dependently
prevented UVB-induced corneal damage or photoker-
atitis by inhibiting the accumulation of NFκB, iNOS,
TNFα and MDA while increasing glutathione levels
in mammals.26 Zerumbone, at 100 mg/kg after UVB
exposure, reduced MDA (lipid peroxidation marker)
levels, while increasing glutathione, glutathione reduc-
tase and SOD (superoxide dismutase) levels in the
lens.26 Zerumbone is known for its protective and ther-
apeutic effects against colorectal, breast, cervical, liver
and other cancers linked to aging.32
Herb is defined in the English Oxford Dictionary as
‘any plant with leaves, seeds, or flowers used for food,
flavoring, medicine, or perfume.’
Herbs Containing Phenolic Compounds
and Catechins
Many leafy herbs, such as basil and Moringa leaf,
contain beneficial phenolics such as catechins and fla-
vonoids that are potent against various oxidative-stress-
related degenerative diseases (Fig. 10.3).31,33–35 The
phenolic compounds often show beneficial effects on
diabetes, hypertension, obesity, cancer, cognition and
visual degeneration.
Oregano (Origanum vulgare)
Origanum majoricum, O. vulgare ssp. hirtum and
Poliomintha longiflora have higher antioxidant ORAC
(oxygen radical absorbance capacity) and pheno-
lic contents than many other culinary and medici-
nal herbs. Oregano retards aging and degenerative
diseases through antioxidant defense mechanisms.36
These antioxidant mechanisms include preventing
oxidation-induced DNA damage and enhancing the
antioxidant response elements and enzymes.37 Other
herbs with very high ORAC values are Catharanthus
roseus, Thymus vulgaris, Hypericum perforatum and
Artemisia annua. Rosmarinic acid was among the most

Normal rat’s bone Architecture of oxidatively Architecture of bone in an

architecture. stressed estrogen-deficient estrogen-deficient rat
rat’s bone. supplemented daily with 300 mg
of catechin-rich botanical
extract/kg body weight in
drinking water.(52)
(H&E staining, 400 × magnification)
FIGURE 10.3  Femur bone architecture of rats after 3 months of estrogen deficiency-induced oxidative stress, with and without catechin-rich
botanical extract supplementation.

2.  ANTIOXIDANTS AND AGING

 Herbs
predominant phenolic compounds in Salvia officinalis,
Thymus vulgaris, Origanum majoricum and P. longiflora,
whereas quercetin-3-O-rhamnosyl-(1→2)-rhamnosyl-
(1→6)-glucoside and kaempferol-3-O-rhamnosyl-(1→2)-
rhamnosyl-(1→6)-glucoside were predominant phenolic
compounds in Ginkgo biloba leaves.38
Vitex negundo
Dietary antioxidative flavonoids from various herbs
and botanical sources are protective against aging and
degenerative ailments. They help to normalize blood
sugar and the lens protein expression of cataract in
animal models. The flavonoids from herbs such as V.
negundo protect against selenite toxicity and cataracto-
genesis in enucleated rodent lenses by maintaining anti-
oxidant status and calcium homeostasis, by protecting
sulfhydryl groups and by decreasing oxidative stress
in the lens.39 In these studies, measures of antioxidant
status included the activities of superoxide dismutase
(SOD), catalase, Ca(2+)ATPase, reduced glutathione
(GSH) concentrations, protein sulfhydryl content, cal-
pains, calcium and thiobarbituric acid-reactive sub-
stances (TBARS).
Moringa oleifera Leaves
Flavonoids from Moringa oleifera leaves were shown
to help retard oxidative-stress-related aging ailments
such as cataractogenesis by (i) enhancing the activities
of antioxidant enzymes (superoxide dismutase and cata-
lase), (ii) reducing the intensity of lipid peroxidation, (iii)
inhibiting free radical generation in rats, (iv) improving
reduced glutathione levels and (v) reducing protein
oxidation.34
Brassica Flavonoids
Flavonoids from (especially) the brassicas prevented
selenite-induced cataractogenesis in albino rat pups
by (i) maintaining antioxidant status and ionic balance
through the Ca2+ ATPase pump and (ii) inhibiting lipid
peroxidation, calpain activation and protein insolubili-
zation.40 The antioxidant status was measured through
superoxide dismutase (SOD), catalase activities, reduced
glutathione (GSH) and the levels of lipid peroxidation
products.
Ginkgo biloba
Ginkgo biloba is used for cognitive dysfunction,
dementia and Alzheimer’s disease. The flavonoid-
rich leaves generally improve cerebral blood flow and
memory. The ginkgolides inhibit platelet aggregation,
while the bilobalide protects against neuronal death
2.  ANTIOXIDANTS AND AGING
103
caused by global brain ischemia and excitotoxicity-
induced damage. The mode of neuroprotection is via
antioxidative, anti-amyloidogenic and anti-apoptotic
effects.41 The antioxidative effects of Ginkgo biloba are
shown by its protective effects against membrane lipid
peroxidation.42 Lipid peroxidation in membranes was
measured by the generation of lipid radicals (using
electron paramagnetic resonance spectroscopy) and
thiobarbituric acid-reactive substances (TBARS).42
However, vitreous hemorrhage was reported with the
use of Ginkgo biloba in a patient with age-related macu-
lar disease.43
Trigonella foenum-graecum Seeds (Fenugreek),
Chili and Pennywort (Centella asiatica)
Alcoholic extract of fenugreek (Trigonella foenum-grae-
cum Linn) seeds (2 g kg-1 day-1) has beneficial effects on
body weight, blood glucose and cataract development in
aging humans.44 The herbs and spices fenugreek, garlic,
ginger, pennywort and red pepper are effective as hypo-
cholesterolemics, and they help to retard oxidation and
age-related cognitive decline and progression of meta-
bolic syndrome.45,46
Saffron (Crocus sativus L.)
Saffron increases blood flow in certain tissues47
affected by aging or chronic oxidative stress. Saffron
consumption before tissue exposure to damaging light
results in neuro-protective effects through the regulation
of various known genes, including the genes encoding
the antioxidative GPx3 and ncRNAs.48 Saffron increases
blood flow in the retina and choroid, improves memory
and learning skills and has antihypertensive, anticonvul-
sant, antitussive, anti-­genototoxic and cytotoxic effects,
as well as anxiolytic, aphrodisiac, antioxidant, antide-
pressant, anti-­nociceptive, anti-­inflammatory and relax-
ant properties.47 ­Saffron is reportedly anti-­carcinogenic,
antimutagenic and analgesic. It shows beneficial effects
on opioid dependence, cardiovascular lipids, the respi-
ratory system, gastric ulcer, the immune system, insulin
resistance, tissue oxygenation and bronchodilation, and
it has antibacterial effects.47
Saffron has antioxidants that are vision protective
and help in the regulation of cell membrane fatty acid
content, making vision cells more resilient. Saffron: (i)
protected the photoreceptors from tissue stress, main-
taining both morphology and function and regulated
cell death, (ii) reduced the rate of photoreceptor death
induced by bright continuous light (BCL) in animals,
(iii) protected the outer nuclear layer (ONL) in a way
similar to that of β-carotene and (iv) prevented the
strong upregulation of FGF2 caused by BCL.49 Saf-
fron prevented vision loss with age, and reversed
104 10.  HERBS AND SPICES IN AGING

FIGURE 10.4  Examples of antioxidative seaweeds.

age-related macular degeneration (AMD) that often SEAWEEDS

causes blindness in old age. Saffron protected photo-
receptors from damage; this inhibited and possibly
reversed AMD and retinitis pigmentosa (a genetic eye
disease). AMD is incurable but can be retarded. When
given a daily saffron pill for 3 months, pensioners with
AMD – which gradually destroys sharp, central vision –
reported improvements in their vision; the effect dis-
appeared when the saffron supplement was stopped.
Dietary saffron protected the eyes from damaging
bright light and eye-related genetic diseases which can
lead to blindness.50
Edible seaweeds or sea vegetables may be considered
as marine herbs that are rich in botanical antioxidants
and beneficial for oxidative stress and health manage-
ment during aging (Figs 10.4, 10.5 and 10.6). Seaweed
compounds that include sulfated polysaccharides,
phlorotannins, carotenoids (e.g. fucoxanthin), minerals,
peptides and sulfolipids are beneficial against various
degenerative metabolic diseases and their therapeutic
modes of action and bioactive components have been
well studied.51

2.  ANTIOXIDANTS AND AGING

 Summary Points 105
FIGURE 10.5  The livers of oxidatively stressed rats
on a prolonged lipogenic diet (with and without supple-
mentation with antioxidative herbs).

Liver of oxidative stress-induced Livers of rodents on a lipogenic diet +

rodents on a prolonged lipogenic diet. antioxidant herbs. The livers were
The liver appeared much paler than slightly pale but were less fatty.(53)
normal, soft, mottled and fatty.

Normal rodent kidney showed Kidney of a rodent on a lipogenic Kidney of a rodent on a

normal glomeruli and tubules diet showed mononuclear lipogenic diet showed
[H&E × 100]. inflammatory cell infiltration and foamy tubular epithelial
thickened glomerular basement cells [H&E × 400].
membranes (glomerulopathy)
[H&E × 100].

Kidney of a rodent on a Kidney of a rodent on a lipogenic Kidney of a rodent on a

lipogenic diet showed loss of diet showed mesangium lipogenic diet + herbs
whole glomerus and tubular expansion [H&E × 400]. showed normal glomerulus
dilation [H&E × 400]. and tubule structures [H&E × 400].
FIGURE 10.6  Representative microscopic appearance of the kidney of oxidative stressed rats, induced by lipogenic diet (with and without
antioxidative herb supplementation). Reproduced with permission from reference.53

SUMMARY POINTS dyslipidemia, oxidative stress, stroke, inflammation,

• T he protective effects of certain herbs and spices
against aging and oxidative stress are reviewed.
• The health conditions covered include cardiovascular
ailments, cancer, obesity, diabetes, hypertension,
allergy, thyroid problems, cognition, infection and
tissue injuries.
• The herbs and spices discussed include cloves,
saffron, turmeric, ginger, oregano, cinnamon, cumin,
black pepper, Vitex negundo, Moringa olefera leaves,

2.  ANTIOXIDANTS AND AGING

106 10.  HERBS AND SPICES IN AGING
fenugreek, onion, garlic, chili, Ginkgo biloba and
seaweeds.
• Some bioactive components of the herbs and spices
responsible for the effects are mentioned.
• Some modes of action of the herbs and spices (mostly
antioxidant, antiglycating, biochemical signaling,
and modulation of gene expression) are compiled.
  
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