Certain Spices Inhibit Beta Secretase Which Slow Accumulation Of Amyloid Beta

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Amyloid beta, the principal component of senile plaques, is thought to be the pathogenesis of Alzheimer’s disease.  The development of Alzheimer’s disease is associated with plaques and tangles in the brain.  These plaques and tangles are referred to as amyloids which are aggregates of proteins that become folded into a shape that allows many copies of that protein to stick together.  The amyloid-cascade hypothesis states that the production and excessive accumulation of amyloid beta is the primary pathological event leading to Alzheimer’s disease.  1

The precursor to amyloid beta is Amyloid Precursor Protein (APP), which is endogenous in brain cells and is inert.  The inert APP is converted by proteolytic enzymes by being cleaved by proteases in the secretase family, namely:  2

One of these three secretase enzymes is beta secretase (or BACE1).  The initial stage of cleaving APP is done by beta secretase. 

Thus a therapeutic strategy for Alzheimer’s disease is to inhibit over expression beta secretase.

A study from 2015 published in the Journal of Natural Medicines focused on the inhibition of beta-secretase from plant resources including herbs and spices.  The researchers screened a number of herbs and spices for their ability to inhibit beta secretase.   They discovered a number of chemical compounds found in a number of spices that were effective in inhibiting beta secretase.  These chemical compounds include:  3

  • alpha-caryophyllene
  • beta-caryophyllene
  • beta-caryophyllene oxide
  • curcumin
  • demethoxycurcumin
  • bisdemethoxycurcumin
  • piperine

Since the molecular weight of these chemical compounds are relatively low, they are able to pass through the blood brain barrier and effect their therapeutic value.

The study identified the spices that contain these 7 chemical compounds, although they are found in other herbs and spices:

Spices Containing Beta Secretase Inhibiting Chemical Compounds

Chemical CompoundSpice
alpha-caryophylleneblack pepper
beta-caryophyllene black pepper
beta-caryophyllene oxidecurry leaf
curcumintumeric root
demethoxycurcumintumeric root
bisdemethoxycurcumintumeric root
piperineblack pepper
Source: DOI: 10.1007/s11418-014-0859-3

Additional information on the 7 chemical compounds:

alpha-caryophyllene

Alpha-caryophyllene, also known as Humulene or alpha-humulene is a naturally occurring monocyclic sesquiterpene that was first found in the essential oils of Humulus lupulus (hops). Alpha-caryophyllene is an isomer of Beta-caryophyllene and both are of found together in aromatic plants.

Alpha-caryophyllene is contained in the essential oils of aromatic plants such as Salvia officinalis (common sage, culinary sage), ginseng species. It is also the characteristic aroma of Cannabis sativa, an interestingly is was shown to be a selective agonist of cannabinoid receptor type-2 (CB2). 1

beta-caryophyllene

Beta-caryophyllene is a natural bicyclic sesquiterpene that is a constituent of many essential oils.  It provides the spiciness to black pepper.

The approximate quantity of caryophyllene in the essential oil of each source is given in square brackets ([ ]):

  • Basil (Ocimum spp.) [5.3–10.5% O. gratissimum; 4.0–19.8% O. micranthum]
  • Black caraway (Carum nigrum) [7.8%]
  • Black pepper (Piper nigrum) [7.29%]
  • Cannabis, hemp, marijuana (Cannabis sativa) [3.8–37.5% of cannabis flower essential oil]
  • Cloves (Syzygium aromaticum) [1.7%-19,5% of clove bud essential oil]
  • Copaiba oil (Copaifera spp.)
  • Hops (Humulus lupulus) [5.1–14.5%]
  • Lavender (Lavandula angustifolia) [4.62% of lavender oil]
  • Malabathrum (Cinnamomum tamala) [25.3%]
  • Oregano (Origanum vulgare) [4.9%-15.7]
  • Rosemary (Rosmarinus officinalis) [0.1–8.3%]
  • True cinnamon (Cinnamomum zeylanicum) [6.9–11.1%]
  • Ylang-ylang (Cananga odorata) [3.1%-10.7%]

Source: Wikipedia - Caryophyllene

beta-caryophyllene oxide

Caryophyllene oxide is similar in structure to beta-caryophyllene and its function in plants is to act as a defence against disease causing microbes, especially fungal microbes.  It is found in in lemon balm (Melissa officinalis) as well as curry leaf (Murraya koenigii (L.) Spreng).

Curry leaf is not the same as curry.  Curry is a complex combinations of spices or herbs, usually including fresh or dried hot chillies, coriander, cumin, and turmeric.  Curry leaf is from the curry tree (Murraya koenigii or Bergera koenigii) and is native to India and Sri Lanka.

Curry leaf contains up to 58 compounds of which the major one is caryophyllene oxide at 16.6%.   1

curcumin, demethoxycurcumin, bisdemethoxycurcumin

Tumeric root contains four curcuminoids, which is the main active ingredients:

  • bisdemethoxycurcumin
  • curcumin
  • cyclocurcumin
  • demethoxycurcumin

Most commercial available preparations of “curcumin” contain approximately 77% curcumin, 17% demethoxycurcumin and 3% bisdemethoxycurcumin. 1

Curcuminoids primarily exist in the curcuma genus with the highest amounts in curcuma longa (tumeric root).  Cucuminoids also exit in Ginger (Zingiber officinale).

piperine

Piperine is found in a number of species in the genus Piper.  It is an alkaloid that is responsible for the pungency of black pepper and long pepper.

Images of the 3 Spices and their chemical constituients that inhibit beta secretase

  • Black Pepper (alpha-caryophyllene, beta-caryophyllene and piperine)

Cover Photo:  Curry Tree (Murraya koenigii (L.) Spreng)