The Science

The Science Behind Pinecone Extract (PCE)

Pine cone extract (PCE) has a medicinal history that dates back to the Greek Physician Dioscorides (A.D. 514). In modern day Japan it is used as a natural remedy to treat illness and disease ranging from the common cold to cancer. There are a wide number of constituents in pine cone extract, including polysaccharides, tannins, lignins and several types of phenolic acids. These bioactive phytochemicals have shown in clinical studies to stimulate an immune response at a cellular level, most notably is an increased antibody production. There are many illnesses that may potentially benefit from treatments that include pine cone extract as part of the protocol.

Research efforts into the medical uses of pine cone extract are ongoing and continuous. Each new set of results expands the line of questioning and broadens researchers’ understanding of how they can help the body heal itself. Published studies indicate that pine cone extract (PCE) inhibits the growth of HIV in human T cell cultures, and even the growth of influenza and the herpes simplex virus. In laboratory tests it has been shown to enhance immunity, inhibit tumor activity, and suppress induction of lymphoma (a type of cancer involving cells of the immune system). There has been more than twenty years of positive research that supports the use of pine cone extract (PCE). It is an invaluable tool in addressing chronic immune deficiency conditions.

Scientific Studies Examining the Benefits of Pinecone Extract:

  • Pine cone extract promotes immune cell development in both human cells and animal models. It has been demonstrated (Bradley, 2003) that the active component of pinecone extract is capable of promoting the rapid differentiation of human peripheral blood mononuclear cells (PBMC) into mature dendritic cells.
  • Dendritic cells are recognized as the most potent antigen-presenting cells of the immune system. Their ability to uptake, process and present antigen to T cells is central to the development of immune responses against bacterial and viral-infected cells, cancer cells and vaccine antigens.
  • Lai et al. (1990) purified the active components of pinecone extract and identified fractions that induced the production of macrophages, a white blood cell that surrounds and kills microorganisms, removes dead cells and stimulates the action of other immune system cells.
  • Other studies (Satoh et al., 1999) showed that pinecone extract inhibited HIV-induced effects on cells in cell culture. Moreover, pretreatment of mice injected with the extract protected them from a lethal infection with E.coli bacteria.
  • Nagasawa et al. (1992) reported the antiviral effect of oral and intravenous delivery of pine cone extract when administered to mice infected with a mouse mammary tumor virus (MMTV). MMTV is normally secreted during lactation, and the extract was able to completely suppress the secretion of virus. The major finding of this study is that oral administration of pine cone extract appears to suppress the production of new virus in an animal model system.
  • Eberhardt and Young (1996) further confirmed the antiviral effects of various extract fractions. In this study, the extract was tested for antiviral activity in a T4 lymphocyte cell (immune cell) line and shown to inhibit virus activity at a concentration of approximately 10 micrograms of extract per milliliter. Importantly, there was no T4 cell toxicity until the pinecone extract dose was over 56 micrograms per milliliter. This demonstrates the safety of pine cone extract and once again suggests that it could be a useful therapeutic agent.
  • Experimental studies have shown that pine cone extract (PCE) suppresses the growth of influenza virus due to interaction between virus proteins and pine cone’s antitumor substances of the extract, thus inhibiting the viral RNA synthesis and suppressing virus multiplication.
  • PCE also has various antitumor substances that significantly inhibit the growth of transplanted tumor cells in mice.
  • Pine cone extract (PCE) has shown to promote, in a dose-dependent manner, the rapid differentiation of human peripheral blood mononuclear cells (PBMC) into mature dendritic cells. This is important because dendritic cells are recognized as the most potent antigen presenting cells of the immune system. Their ability to uptake, process, and present antigen to T cells is central to the development of immune responses against bacterial- and viral-infected cells, cancer cells and vaccine antigens.
  • Pine cone extract has shown in human T cell cultures to inhibit HIV replication by binding to the viral reverse transcriptase and can additionally inhibit HIV gene transcription.

The effects of pine cone extract are published in high quality peer-reviewed journals by independent university research scientists.

Medical Research in Regards to Pinecone Extract

Pinecone Extract Anti-Viral Properties 

1- Interaction between influenza virus proteins and pine cone antitumor substance that inhibits the virus multiplication

Watanabe K, Momose F, Handa H, Nagata K

"Fractions obtained from pine cone extract (PCE) of Pinus parviflora Sieb. et Zucc. have been shown to suppress the growth of influenza virus…"

In Vivo. 1992 Sep-Oct; 6(5): 491-5 Biochem Biophys Res Commun. 1995 Sep 14; 214(2): 318-23

2- Anti-influenza virus activity of a lignin fraction from cone of Pinus parviflora Sieb. et Zucc.

Sakagami H, Takeda M, Kawazoe Y, Nagata K, Ishihama A, Ueda M, Yamazaki S

"…the infectivity of virus that had been pre-incubated with a lignin prepared from cones of Pinus parviflora Sieb. et Zucc. was significantly reduced… These data suggest that [this lignin] either inactivates the virus or induces the anti-viral state in cells by binding to virions or cells."

Antiviral Res. 1991 Jan; 15(1): 41-9

3- Possible involvement of lignin structure in antiinfluenza virus activity

Harada H, Sakagami H, Nagata K, Oh-hara T, Kawazoe Y, Ishihama A, Hata N, Misawa Y, Terada H, Konno K

"The data suggest that the polymerized phenolic structure of lignified materials is responsible for the anti-influenza A virus activity [of pine cone extract]."

Antiviral Res. 1990 Jan; 13(1): 11-21

4- Inhibition of influenza virus infection by pine cone antitumor substances

Nagata K, Sakagami H, Harada H, Nonoyama M, Ishihama A, Konno K

"The anti-influenza virus activity of polysaccharides and other high molecular weight fractions from pine cone extract (PCE) of Pinus parviflora Sieb. et Zucc. was investigated… These results suggest that PCE, which has been shown to contain antitumor substance(s), also contains anti-influenza virus substance(s)."

Anticancer Res. 1992 May-Jun; 12(3): 845-7

5- Suppression by a pine cone extract of Pinus parviflora Sieb et Zucc of mammary tumor virus in milk of mice

Nagasawa H, Iwai Y, Iwai M, Suzuki A, Imai S

"[Pine cone extract] prevented an increase in milk levels of mouse mammary tumor virus…"

Proc Natl Acad Sci U S A. 1991 Mar 15; 88(6): 2249-53

Pinecone Extract Anti-HIV Properties

1- A soluble factor induced by an extract from Pinus parviflora Sieb et Zucc can inhibit the replication of human immunodeficiency virus in vitro

Tamura Y, Lai PK, Bradley WG, Konno K, Tanaka A, Nonoyama M

"We showed that an extract (PC6) from cones of Pinus parviflora Sieb et Zucc induced the human T-cell line CEM to produce a pepsin-sensitive soluble factor(s) that could inhibit the replication of the type 1 human immunodeficiency virus (HIV-1) in CEM T cells, in U-937 histocytes, in THP-1 monocytes, and in mitogen-activated human tonsillar mononuclear cells… The anti-HIV-1 factor induced by PC6 may be novel…"

AIDS Res Hum Retroviruses. 1991 Mar; 7(3): 349-57

2- Inhibition of human immunodeficiency virus forward and reverse transcription by PC6, a natural product from cones of pine trees

Takayama H, Bradley G, Lai PK, Tamura Y, Sakagami H, Tanaka A, Nonoyama M

"We have previously shown that PC6, a natural product extracted from cones of Pinus parviflora Sieb et Zucc, can inhibit the replication of human immunodeficiency virus type 1 (HIV-1) in CD4+ T cells and in monocyte/macrophage cell lines. Here, we show by immunoprecipitation of HIV-1 proteins with a specific pooled serum that PC6 inhibited the expression of all HIV-1 proteins in CEM cells…"

AIDS Res Hum Retroviruses. 1990 Feb; 6(2): 205-17

3- Modification of human immunodeficiency viral replication by pine cone extracts

Lai PK, Donovan J, Takayama H, Sakagami H, Tanaka A, Konno K, Nonoyama M

"We have shown previously that two fractions (PC6 and PC7) extracted from cones of the Japanese white pine Pinus parvifloria Sieb. et Zucc have potent immunopotentiating effects. Here, we show that PC6 and PC7 inhibited HIV-1 replication (greater than 95%), in a dose-dependent manner, in chronically infected CR10/HIV-1 cells and in acute cytolytic HIV-1 infection of CEM cells. Treatment of CEM cells, prior to or after acute infection with HIV-1, reduced subsequent viral production, but the best inhibitory effect was obtained with treatment before and after infection: an 80% inhibition was achieved with as little as 3 micrograms/ml of PC6. Comparable results were also obtained when PC6 was used to inhibit HIV-1 replication in the U937 human histiocytic lymphoma cell line. Both PC6 and PC7 were relatively nontoxic to cells. The anti-HIV-1 effect of PC6 and PC7 we observed in this report, coupled with earlier reports of their immunopotentiating properties suggest their potential as ideal therapeutic agents for the treatment of AIDS."

In Vivo. 1990 Jan-Feb; 4(1): 7-12

Pinecone Extract Anti-Microbial Properties

1- Antimicrobial spectrum of lignin-related pine cone extracts of Pinus parviflora Sieb. et Zucc.

Oh-Hara T, Sakagami H, Kawazoe Y, Kaiya T, Komatsu N, Ohsawa N, Fujimaki M, Tanuma S, Konno K

"Pinecone… extracts were tested for ability to induce antimicrobial activity in mice infected with Staphylococcal aureus., Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Candida albicans, or Salmonella enteritidis. These alkaline extracts were potent against the first 5 of these strains of microorganisms…"

Anticancer Res. 1988 Jul-Aug; 8(4): 581-7

2- Induction of antimicrobial activity by antitumor substances from pine cone extract of Pinus parviflora Sieb. et Zucc.

Harada H, Sakagami H, Konno K, Sato T, Osawa N, Fujimaki M, Komatsu N

"Pretreatment with two distinct antitumor substances extracted from pine cone of Pinus parviflora Sieb. et Zucc. Protected mice from the lethal effects of E. coli infection… The results suggest a significant role… for the expression of antimicrobial activity induced by pine cone extracts."

In Vivo. 1989 Nov-Dec; 3(6): 359-62

Pinecone Extract Anti-Parasitic Properties

1- Induction of antiparasite activity by pine cone ligninrelated substances

Abe M, Okamoto K, Konno K, Sakagami H

"Pretreatment with two distinct lignin-related antitumor substances extracted from pine cone of Pinus parviflora Sieb. et Zucc. protected infant mice from… infection… [and had] significant antiparasite effects…"

Anticancer Res. 1987 Nov-Dec; 7(6): 1153-9

Pinecone Extract Antioxidant Properties

1- Ascorbyl radical scavenging activity of polyphenols

Satoh K, Sakagami H

"A variety of tannin and lignin-related compounds were compared for their ability to modify the ascorbyl radical intensity of sodium ascorbate. Hot-water extracts prepared from green tea, black tea and pine cone (Pinus parviflora Sieb. et Zucc.), and various wines potently scavenged ascorbyl radical intensity…"

Anticancer Res. 1996 Sep-Oct; 16(5A): 2885-90

Pinecone Extract Anti-Tumor and Anti-Mutagenic Properties

1- Antitumor activity of polysaccharide fractions from pine cone extract of Pinus parviflora Sieb. et Zucc.

Sakagami H, Ikeda M, Unten S, Takeda K, Murayama J, Hamada A, Kimura K, Komatsu N, Konno K

"Hot water extract of pine cone (PCE) of Pinus parviflora Sieb. et Zucc. dose-dependently suppressed both solid and ascites tumor cells transplanted into various mice. Acidic polysaccharides of PCE significantly increased the survival time of mice bearing ascites tumor cells… One of the four polysaccharide fractions… significantly suppressed the growth of solid tumor cells, with occasional tumor regression and necrosis… All acidic polysaccharides were able to activate mouse macrophage-like [white blood cells]…"

Anticancer Res. 1989 Nov-Dec; 9(6): 1593-8

2- Molecular species of the antitumor and antiviral fraction from pine cone extract

Sakagami H, Oh-Hara T, Kaiya T, Kawazoe Y, Nonoyama M, Konno K

"The most active fraction (Fr. VI) of antitumor and antiviral pine cone extract was subjected to chemical structure analysis… A commercial alkali-lignin showed antiviral activity and granulocyte iodination stimulating activity as effective as those of Fr. VI, but had much weaker immunopotentiating activities, such as antitumor and antimicrobial activities and splenocyte [white blood cell] stimulating activity…"

Mutat Res. 1993 Jul; 297(1): 53-60

3- Interaction of pine cone extract fraction VI with mutagens

Lee H, Aoki K, Sakagami H, Yoshida T, Kuroiwa Y

"Pine cone extract… shows indirect [and direct] antimutagenicity…"

Anticancer Res. 1992 Mar-Apr; 12(2): 501-3

4- Inhibitory effect of lignin-related pine cone extract on cell proliferating enzyme activity of spontaneous mammary tumors in mice

Nagasawa H, Sakamoto S, Sawaki K

"… All results suggest that these lignin-related compounds [from cone extract of pine (Pinus parviflora Sieb et Zucc)], may be useful as chemopreventive [anti-cancer] agents…"

Int Immunopharmacol. 2003 Feb; 3(2): 209-23

Pinecone Extract immune System Support Properties

1- The novel differentiation of human blood mononuclear cells into CD1a-negative dendritic cells is stimulated in the absence of exogenous cytokines by an extract prepared from pinecones

Bradley WG, Widen RH, Weiser AM, Powers JJ, Fountain LB, Punjwani P, Lofgren SM, Hadzic T, Klein R, Green WH, Tanaka A

"The production of dendritic cells, both in-vivo and in-vitro, has become the intense focus of research activities. Common to many of these production protocols is the use of cytokines, typically granulocyte-monocyte colony stimulating factor and either interleukin 4 or tumor necrosis factor alpha or a combination of all three. Herein, we report our findings that a proprietary pinecone extract is capable of in a dose-dependent manner, and in the absence of exogenous cytokines, the rapid differentiation from peripheral blood mononuclear cells of mature CD1a-negative dendritic cells."

Anticancer Res. 1991 Mar-Apr; 11(2): 841-5

2- Stimulation of mouse peritoneal macrophages [white blood cells] by lignin-related substances

Kikuchi K, Sakagami H, Fujinaga S, Kawazoe Y, Oh-Hara T, Ichikawa S, Kurakata Y, Takeda M, Sato T

"Various lignified materials, including pine cone extract and a commercial lignin, stimulated the morphological change (spreading) of mouse peritoneal macrophages [white blood cells], and their functional maturation…"

Adv Exp Med Biol. 1992; 319: 331-5

3- Multiple immunological functions of extracts from the cone of Japanese white pine, Pinus parviflora Sieb. et Zucc.

Sakagami H, Konno K, Kawazoe Y, Lai P, Nonoyama M

Anticancer Res. 1991 Mar-Apr; 11(2): 881-8

4- Antitumor, antiviral and immunopotentiating activities of pine cone extracts: potential medicinal efficacy of natural and synthetic lignin-related materials (review)

Sakagami H, Kawazoe Y, Komatsu N, Simpson A, Nonoyama M, Konno K, Yoshida T, Kuroiwa Y, Tanuma S

"Several antitumor substances that effectively inhibited the growth of ascites and solid tumor cells transplanted in mice were isolated from pine cone… These antitumor substances were also potent antiviral agents against human immunodeficiency virus, herpes simplex virus and influenza virus; they induced antimicrobial activity against Staphylococcal aureus, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae and Candida albicans, and induced antiparasite activity against Hymenolepis nana in mice…"

Anticancer Res. 1989 Jul-Aug; 9(4): 961-6

5- Mitogenic activity of pine cone extracts against cultured splenocytes [white blood cells] from normal and tumor-bearing animals

Kurakata Y, Sakagami H, Takeda M, Konno K, Kitajima K, Ichikawa S, Hata N, Sato T

"An acidic pine cone extract, Fr. V. of Pinus parviflora Sieb. Et Zucc. significantly stimulated DNA synthesis of isolated splenocytes [white blood cells] from both mice and rats, but only marginally affected the DNA synthesis of leukemic cell lines…"

J Leukoc Biol. 1989 Feb; 45(2): 168-75

6- Stimulation of granulocytic cell iodination by pine cone antitumor substances

Unten S, Sakagami H, Konno K

"Antitumor substances (Fractions VI and VII) prepared from the NaOH extract of pine cone significantly stimulated the iodination (incorporation of radioactive iodine into an acid insoluble fraction) of human peripheral blood adherent mononuclear cells, polymorphonuclear cells (PMN), and human promyelocytic leukemic HL-60 cells. In contrast, these fractions did not significantly increase the iodination of nonadherent mononuclear cells, red blood cells, other human leukemic cell lines (U-937, THP-1, K-562), human diploid fibroblast (UT20Lu), or mouse cell lines (L-929, J774.1)…The stimulation activity of these fractions was generally higher than that of various other immunopotentiators…"

Biosci Biotechnol Biochem. 2007 May; 71(5): 1342-4. Epub 2007 May 7